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THE 



INCIDENTAL 



EFFECTS OF DRUGS 



PHARMACOLOGICAL /ND CLINICAL HAND-BOOK 



DR. L. LE WIN 

ASSISTANT AT THE PHARMACOLOGICAL INSTITUTE OF THE UNIVERSITY OF BERLIN 







TRANSLATED BY 



V 



W. T. ALEXANDER, M.D. 



tp 




NEW YORK 
WILLIAM WOOD & CO M P A N Y 



v 



Copyright by 

WILLIAM WOOD & COMPANY. 

1882. 



STEAM PRESS OF 

H. O. A. Industrial School, 
189 E. 76TH Street. 



TRANSLATOR'S PREFACE. 



A recognition of the importance of a knowledge of the 
incidental, accidental, or unexpected effects (Nebenwirkun- 
gen) of drugs upon the various organs and systems of the 
body, has led the translator of this manual to believe that 
it will prove of interest and advantage to a larger number 
of readers than it can obtain in its original form alone. 
The literature of the subject of which it treats, as far, at 
least, as he is familiar with it, is comparatively meagre, the 
only systematic work upon it being one confined to the 
study of a single organ, viz., a portion of the interesting 
book of Dr. H. G. Piffard, upon the " Materia Medica and 
Therapeutics of the Skin." 

In view of the active interest which is at present taken 
in the study of materia medica and therapeutics, especially 
in this country, it is to be hoped that others may be stimu- 
lated to study and record with more care than in the 
past the peculiar actions of drugs upon individual 
organs. W. T. A. 



PREFACE. 



The science of materia medica, as an essential connect- 
ing link between purely experimental investigation and 
empiricism, receives contributions both from the labora- 
tory and from observation at the bedside. The facts ob- 
tained from these sources present in their totality the 
picture of the typical mode of action of individual drugs. 

But in the therapeutic employment of certain drugs, de- 
viations sometimes occur from this typical and, as one 
may say, normal action, whose recognition and correct in- 
terpretation are not always easy. A knowledge of them 
is, however, of great importance to the physician, since 
they may, in a given case, shed light upon the cause of the 
unexpected phenomena which show themselves, and also 
furnish indications to guide him in his practical interfe- 
rence. 

The individual facts bearing upon this subject, the phe- 
nomena of abnormal drug-action, are widely scattered 
through medical literature, and are either not at all men- 
tioned, or are only superficially treated of in text-books on 
materia medica and therapeutics. For this reason I have 
for a long time occupied myself in collecting and anno- 
tating them, and in making additions to their number 
from my own experience. The result is contained in this 
w T ork, which will, I hope, not only satisfy practical require- 
ments, but also stimulate to further observations in this 
direction. L. Lewin. 

Berlin, January, 1881. 



CONTENTS. 



PAGE 

Introduction I 

Tonics 29 

Astringents 51 

Acids * 70 

Alteratives *77 

Excitants 131 

Narcotics 134 

Evacuants 196 

Purgatives 196 

Emetics '. 200 

Diuretics 206 

Expectorants 207 

Antiparasitics 208 

Sudorifics , 215 

Emollients 221 

Rubefacients and Vesicants , .222 



A 



The Incidental Effects of Drugs. 



INTRODUCTION. 



Drugs act locally in the animal economy , i. c, they 
influence exclusively, or in a particular manner, according 
to their chemical or physical properties, certain classes of 
cells or cellular structures. " Certain substances have 
affinities for certain parts of the body " is an axiom first 
enunciated by Virchow, 1 upon which it follows as a natu- 
ral consequence, that certain drugs, in addition to their 
curative effects, may, by either a direct or reflex action, 
produce symptoms affecting homologous or heterologous 
cell-groups which, for therapeutic purposes, should not be 
acted upon. After the administration of opiates, for 
instance, not only is an influence exerted upon the central 
nervous system, but also upon peripheral nerve-centres 
and nerves, so that, in addition to a more or less pro- 
nounced hypnotic effect, there occurs a temporary paraly- 
sis of the nerves which regulate the movements of the 
intestines, and in consequence of this, a stagnation of the 
intestinal contents. When tartar emetic is taken, vomit- 
ing occurs in consequence of irritation of the gastric 
mucous membrane, and at the same time, the activity of 

Virchow: Specificer und Specifisches, Archiv f. path. Anatomie, Bd. vi., 
p. 24. 

I 



2 INCIDENTAL EFFECTS OF DRUGS. 

the heart is lessened by the direct action of the drug upon 
its substance. The inhalation of chloroform produces an 
effect upon the nerve-centres, particularly the cerebrum, 
and, by a reflex action from the respiratory mucous 
membrane, the action of the heart is also interfered with. 
While, therefore, homogeneous elements of a nervous 
nature, in different regions of the body, are affected 
by opium and chloroform, the antimony in tartar emetic 
exerts its influence upon heterogeneous tissues, viz., 
mucous membranes and muscles. In an analogous man- 
ner, substances which possess the inherent power of 
influencing a still greater number of cell-forms, may pro- 
duce a whole chain of pathological symptoms. Such 
effects as these are, however, regarded as physiological, 
because while inseparable from one another, they belong 
in their totality to the action of the drug. The individ- 
ual symptoms are only separated from each other when, 
in accordance with the therapeutic indication for the 
drug, it becomes desirable to distinguish between pri- 
mary and incidental action. 

§ 2 - 

Although, in this manner, nearly all active drugs exert 
the influences peculiar to themselves upon certain groups 
of cells, e. g., a diseased organ, and thus bring about cura- 
tive results, it not infrequently happens that in the cases 
of certain persons, the desired local effect is not produced, 
the drug proving itself " inactive." Thus, chloroform 
may fail to produce anaesthesia, quinine to reduce a swol- 
len spleen, and cathartics, even those belonging to the 
class of drastics, to cause an evacuation. 

If the drugs used be of good quality (which in this case 
is taken for granted), the cause of this anomalous result 
can lie only in the person taking the remedy. His organ- 
ization, or the structure of the healthy or diseased parts 
upon which it is desired to act, must be different from that 



INTRODUCTION. 3 

of the same parts in other persons. The same postulate must 
be advanced for such individuals as possess an organization 
exceptional as regards its capacity for resisting disease, in 
consequence of which they are never attacked by certain 
contagious maladies, e. g., exanthematic typhus. In the 
latter, as in the former cases, the immunity may be due, 
not to gross anomalies of structure, which will be dis- 
cussed later at greater length, but to physiological differ- 
ences in tissues or organs. 

It will be readily understood that, if certain organs of 
an individual fail to respond to the action of certain drugs 
which ordinarily produce well-known functional effects, 
therapeutical experiments with these drugs may lead to 
erroneous conclusions, when made upon such persons. 
This fact may perhaps explain the often diametrically 
opposed results which follow the use of a given drug in 
different persons. 

§3- 

Of far greater importance to the physician than the 
non-occurrence of a normal drug effect, are the not infre- 
quently observed incidental effects of remedies, which either 
take the place of the normal action, or appear simul- 
taneously with it. The administration of quinine, for 
instance, is not uncommonly followed by the appearance 
of a polymorphous exanthema, or, in very rare cases, 
intense effects upon the organ of vision, manifested by 
permanent amaurosis. The usually somewhat inert cod- 
liver oil may cause vesicular eruptions, iodide of potassium 
induce hypersecretion from the ocular and nasal mucous 
membranes, and salicylic acid excite, among other effects, 
sweating and phenomena of irritation of the nervous sys- 
tem. 

Many different designations for the anomalous symp- 
toms produced by drugs are found in literature. In Ger- 
many, they were and are still called " Nebenwirkungen," 



4 , INCIDENTAL EFFECTS OF DRUGS. 

" physiologische Nebenwirkungen," " Arzneisymptome," 
also accidental, or special, or peculiar effects. French 
authors designate them " inconvenients," or "inconve- 
nients therapeutiques," also, " accidents," or " cas d'acci- 
dents." In England, they are sometimes called " acciden- 
tal poisoning." 

Writers have always hesitated to regard these incidental 
effects as toxicological, and with justice, for we are not 
warranted in pronouncing one or more symptoms, which 
do not appear in a thousand cases after taking a drug, to 
be the result of poisoning when they show themselves in 
the next case. It is further to be remembered that the 
majority of these incidental effects in no wise correspond 
to the symptoms produced by a poisonous dose of the 
same drug, and that we cannot produce them at will, 
especially those affecting the skin. These appear only 
under definite individual conditions, and are, therefore, 
almost beyond the reach of experimental provocation. 
Up to the present time, there has been no lack of physi- 
cians thoroughly imbued with humoral-pathological 
ideas, who, in given cases, attribute a certain teleological 
significance to the appearance of incidental drug effects, 
such as was formerly claimed, e. g., for hemorrhage from 
the hemorrhoidal vessels. In the same manner as it was 
then regarded as a fortunate circumstance that the 
" anima " which presided over the vascular system should 
have chosen the hemorrhoidal vessels for the elimination 
of "impurities" from the body, were the "drug symp- 
toms," particularly those affecting the skin, considered as 
the expression of a struggle between the drug and the 
morbid humors of the blood, by which the latter, either 
through functional changes or material anatomical lesions, 
gave evidence of their subjection or their elimination from 
the body. 

In opposition to this vitalistic humoral-pathological 
aspect of the subject, another hypothesis has been ad- 



INTRODUCTION. 5 

vanced to explain the occurrence of incidental drug- 
effects, as well of those which are the almost constant 
attendants upon every drug-action, as of those which 
dnly occasionally appear. Their causes may be either pe- 
culiar to the individual, or dependent upon temporal or local 
influences, or the quality of the drug. The former shall be 
first considered. 

§4. 

The peculiarity of each individual, as compared with 
others, may be permanent or of limited duration. It is 
most strikingly manifested when the person is exposed to 
the manifold occasional causes of disease. The same 
external noxious influence acting upon the organism is 
capable of producing such different effects upon different 
individuals, that while some are affected to a scarcely 
appreciable extent, others are only temporarily injured, 
and others again experience permanent functional de- 
rangements. Individual susceptibility to external influ- 
ences varies, therefore, within wide limits. It may be 
so great that causes belonging to the domain of physiol- 
ogy may be capable of producing pathological manifesta- 
tions. The smelling of a rose, the tasting of a strawberry, 
etc., may cause in certain persons nervous disturbances or 
changes in the skin (thus proving the existence of a condi- 
tion called heightened individual irritability or idiosyn- 
crasy), while the immense majority of persons are in no 
wise affected by such agencies. 

Analogous appearances sometimes show themselves 
after the external or internal use of certain drugs. The 
extract of Calabar bean, instilled into the eye, causes in 
certain persons only a burning sensation in the conjuncti- 
val sac and increased lachrymation ; morphia, taken inter- 
nally, causes spasm of the accommodation in excitable 
subjects only, and pilocarpine, in certain cases and in cer- 
tain doses, induces profuse sweating, while others, after 



6 INCIDENTAL EFFECTS OF DRUGS. 

the same doses, experience a scarcely perceptible increase 
of this function. Here we see, under conditions otherwise 
similar, variations in the influence of external agencies 
upon homologous tissues, which can only be explained upon 
the ground of the existence of individual peculiarities. 

To the question, what is the nature of these peculiarities ? 
it is impossible to give an entirely satisfactory answer. 
Only recently have comparative investigations been under 
taken into the physical behavior of certain organs, the 
heart, blood-vessels, intestines, etc., in individuals of differ- 
ent sexes and ages, in the hope of arriving at a compre- 
hension of so-called constitutional peculiarities. 

There are furthermore, as we shall see later, a number 
of physiological processes going on in the body, which 
render it under certain circumstances peculiarly predis- 
posed to disease, and we are familiar with pathological 
conditions of so trivial a nature that they pass unrecog- 
nized during life, but which render the individual in 
whom they occur highly susceptible to irritation. But 
do all these factors suffice to explain " the mystery of 
individuality," as Virchow calls it ? Certain] v not ! When 
we recall only a few of the minutiae which must be taken 
into account, e. g., the infinitely great differences in the 
distribution of blood-vessels in organs, the multiform 
arrangement of glandular tissues in glands, the deviations 
in innervation of organs, the differences in size of indi- 
vidual nerves and in the distribution of nerve-plexuses, the 
variations in the gross and histological construction of the 
same muscles in different individuals, we must confess, that 
not only is our present ignorance great, but that it will 
always continue. It is nevertheless wrong to entirely 
ignore the existence of individuality, or to deny its im- 
portance. " The possibility of explanation," as Virchow 
says, "is no test of knowledge, for we know many things 
empirically whose causes we cannot comprehend. No exact 
investigation, either anatomical or physiological, patho- 



INTRODUCTION. 7 

logical or therapeutical, has ever succeeded in lifting the 
veil which conceals the conditions governing individual 
peculiarities. In all times it has been regarded as the pecu- 
liar prerogative of exceptionally gifted spirits or of great 
experience to possess that subtle insight which enables 
one to recognize, even approximately, the specific charac- 
ter of the individual." 

It is so well known as to hardly need mention, that 
since the existence of medicine as a practical and 
descriptive art, constitutional peculiarities have been ap- 
preciated and made the object of investigation. The doc- 
trine of temperaments, the recognition of the sanguine, 
phlegmatic, and melancholic constitutions, under the 
hypothesis, that in accordance with the preponderance in 
the body of the blood, bile, mucus, and black bile, individual 
peculiarities are established, was for centuries the firm 
foundation which remained standing after the disappear- 
ance of all other medical theories, and although, as the 
quintessence of humoral pathology, the doctrine is highly 
one-sided and rests upon a false basis, it is still in complete 
harmony with the effort to properly appreciate subtle 
individual peculiarities. 

The factors to be considered in the study of the latter 
cannot be of a gross nature. This is especially true of the 
specific peculiarities of particular organs. If anything is 
essentially calculated to support the dictum of Virchow 1 
that " the reaction of the tissues does not depend primarily 
upon external influences, but upon their intimate struc- 
ture," it is the individual peculiarities which the tissues of 
certain persons manifest under the influence of drugs. 
The application of the tincture of iodine to the skin pro- 
duces usually only an erythema, and yet there are persons 
upon whom the same preparation causes vesiculation and 

1 Virchow: Krankheitswesen und Krankheitsursachen. Archiv f. path. Anat., • 
Ed. 79, Heft i., p. 10. 



8 INCIDENTAL EFFECTS OF DRUGS. 

extensive oedema. Even an absolutely inert ointment, 
made out of any fresh fat, may cause inflammation when 
rubbed upon the skin of some persons. In such cases, the 
cause of the unusual effect can only be the existence of 
subtle alterations in the component parts of the skin, 
which are physically and chemically unrecognizable. The 
difficulty of regarding such great functional differences as 
the consequence of slight variations in the structure of the 
organ in question, is easily overcome when we consider 
the differences in the chemical and physical behavior of 
isomeric bodies, i. e., those which contain the same ele- 
ments united in the same proportions. In these, a change 
in the relative position of certain molecules produces so 
great a difference in their character that they seem essen- 
tially distinct from each other. Nevertheless, in them the 
number of atoms of carbon, hydrogen, and oxygen is 
always the same, as in pyrogallic acid and phloroglucin, 
hydroquinone, resorcin, and pyrocatechin. The behavior 
of allotropic bodies may here also be recalled. These, 
probably on account of differences in molecular arrange- 
ment, although of identical chemical composition, manifest 
widely differing physical characteristics, as in the well- 
known case of carbon in the form of the diamond, gra- 
phite, and coal. 

It is easy to imagine that certain organs in certain per- 
sons are so constituted that, although of the same chemical 
composition, and even the same histological structure, they 
are nevertheless so different from others that they respond 
to a trivial irritation, or show an abnormally intense reac- 
tion under ordinary stimulation. 

§5- 

We have hitherto considered only individuals or organs 

in their varying relations to others of the same kind. 

Although the differences which we have thus far found to 

exist are extraordinarily great, they are nevertheless ex- 



INTRODUCTION. g 

ceeded by those manifested by similar and dissimilar organs 
in the same individual tinder the influence of external agencies, 
especially those of a medicinal nature, without regard to 
whether the action is primary, or secondary and reflected. 

Even the physiological working power of certain simitar 
organs may be different. The lifting power of a gastroc- 
nemius muscle of one side is seldom, under the same 
external conditions, identical with that of the muscle of the 
other side, or the irritability of a nerve equal to that of the 
corresponding nerve. The explanation of this fact is to be 
sought in the natural differences in size of the functional 
elements of the parts, one muscle containing more primi- 
tive fibres than its fellow, and one nerve more nerve-fibres 
than the other, or it may depend upon their relative de- 
gree of development. This latter condition may be readily 
recognized in the greater size of the muscles of the more 
used right extremities in comparison with those on the 
left side of the bod} 7 . 

The fact is further to be recognized that similar, but not 
corresponding portions of the body, as for example, differ- 
ent groups of muscles, may, from the same causes, present 
differences of action, without being the subject of disease. 
Thus, a given volume of a deltoid muscle will surpass in 
working power a similar volume of the intercostal muscles. 

We know that while the cardiac branches of the pneu- 
mogastric nerve can be excited only by very powerful 
electric currents, the pulmonary branches of the same 
nerve show an unusual excitability. Still more striking 
are the differences between structures into whose forma- 
tion tissues of different kinds enter, e. g., the joints. One 
is readily inclined to believe that in this case complete 
identity exists as regards the arrangement of the individual 
constituents, and a similarity as regards reaction against 
external influences. This is, however, not the case. Such 
complex structures as these, made up, in the instance cited, 
of muscle, connective tissue, cartilage and bone in widely 



10 INCIDENTAL EFFECTS OF DRUGS. 

varying proportions, and presenting the greatest diversity 
as regards richness of vascular and nervous supply, are not 
to be placed in the same category, and are certainly not to 
be regarded as of equal functional importance. 

This is most distinctly manifest, when in diseased condi- 
tions of such parts it is desired to produce therapeutic 
effects upon them by a particular drug. Even when direct 
applications are made, unexpected differences show them- 
selves. In this connection, an observation of Senator 1 is 
very instructive. He found that, after the injection of car- 
bolic acid into the joints in acute rheumatism, the benefi- 
cial effects appeared first in the shoulder, later in the knee, 
hand and elbow, and last in the hip. In discussing the sub- 
ject, Senator mentions as factors probably instrumental in 
producing these singular results: anatomical differences, the 
number and arrangement of the vessels, or simply unknown 
peculiarities of structure of the joints, without, however, 
being willing to pronounce definitely for the one or the 
other. The possibilities to be here taken into consideration 
are so numerous, and we are so far from being able to com- 
prehend even the smallest part of them, that we must con- 
tent ourselves for the present with studying them with the 
utmost possible care. 

But even if, in a given case, we had demonstrated, e.g., an 
abnormal arrangement of the vessels of the right shoulder- 
joint as compared with the left, or a more abundant inner- 
vation of the knee than of the elbow-joint, we would still 
only be able to form a conjecture to explain why the same 
agent should produce different results when applied to these 
parts, why it should cure one person and do harm to another. 

If this inquiry be still further pursued, it will be found, 
that in specially predisposed, luckily rarely encountered 
persons, the simultaneously appearing favorable and unfa- 
vorable effects of a drug upon different organs are so 

1 Senator, Berl. Klin. Wochenschrift, 1876, p. 70 



INTRODUCTION. II 

closely connected that the more desirable cannot be ob- 
tained without the undesirable. We know of cases in 
which the employment of iodide of potassium for the pur- 
pose of producing- a diminution in volume of hyperplastic 
glands, as the cervical lymphatic or the thyroid, etc., pro- 
duced the desired effect, and at the same time, a serious 
atrophy of glands previously healthy, as the mammae or 
testes. Such a change can, however, only be due to the 
fact that those organs, which to our appreciation seemed 
normal, had already widely departed from the standard of 
health. Only an abnormality in their intimate structure 
can allow them to be influenced by an agent which does 
usually not produce such effects. 

§6. 

The differences thus far considered in the reaction mani- 
fested by certain individuals, or single tissues of the same 
organism, towards certain medicinal influences, were found 
to depend upon a constitutional predisposition in the econ- 
omy, either congenital, or acquired and become unalterable. 

There is also a predisposition limited as regards time. 
This may be due either to the presence in the body in excess, of 
cliemical substances which render more soluble than usual the 
medicinal agents introduced, or which enter into combination 
with them, thus forming new and directly deleterious agents, or 
it may depend upon pre-existing pathological changes in organs, 
or diseases of the regulatory apparatus. 

With regard to the first explanation, it is well to con- 
sider the apposite observations of Mialhe. 1 This author 
designates the abnormal reaction to medicinal agents due 
to " differences in composition of the animal fluids," as 
" chemical idiosyncrasy," as distinguished from " the idio- 
pathic idiosyncrasy," which is to be regarded as the ex- 
pression of differences in the structure of tissues. It is, 

1 Mialhe: Die Receptirkunst, ubers. von Biefel, Breslau, 1852, p. 239. 



12 INCIDENTAL EFFECTS OF DRUGS. 

for instance, well known that, under some circumstances, 
insoluble substances, as the oxides of iron, zinc, kermes min- 
eral, etc., may produce in the body effects differing widely 
from those which usually follow the administration of these 
drugs, i. e., they may produce injurious effects. The ex- 
planation of this is found in the excessive quantity of acid 
present in the stomach, in consequence of which a larger 
amount than usual of the metals is dissolved. This differ- 
ence in the fluids, which may be regarded as the expres- 
sion of a local disturbance, is entirely distinct from a true 
humoral-pathological dyscrasia, owing to the fact that it 
is of a transitory nature, and is often amenable to correc- 
tion by chemical or dietetic means. 

The recognition of the possibility of such a condition of the 
stomach renders easy, in a given case, the comprehension 
of certain drug effects. Opinions have differed until now, 
for instance, as to the reason why the much-used subnitrate 
of bismuth, even in quite small doses, sometimes causes 
violent local irritative phenomena in the stomach and intes- 
tines, such as vomiting, diarrhoea, etc., as well as general 
manifestations, while in other cases large doses, 4 to 6 grams, 
( 3 i- 3 iss.) produce no abnormal effects. 

It has been definitely established that the presence of 
lead or arsenic in the bismuth, which was generally be 
lieved to be the cause of these untoward results, cannot be 
so regarded, since they are present in too small quantities. 
It is much more probable that these effects are due to the 
quantity of acid present in the stomach. If this be more 
than normal, the intrinsically harmless basic salt may be 
converted into the corrosive neutral body, or in consequence 
of the action of water upon the latter, into the poisonous 
acid salt, and the absorption of the metal, with its local as 
well as its general toxic action, be thus rendered possible. 
That the stomach at different times, according to the indi- 
viduality of the person, the food consumed, the condition 
of digestion, etc., may contain different quantities of acid, 



INTRODUCTION. 1 3 

is a fact which can be so easily determined clinically and 
experimentally that it hardly requires further proof. 

This is also true of the intestinal juices. The greater 
or lesser degree of alkalinity which they present is of im- 
portance in the solution of a great many mineral and veg- 
etable substances, and when their reaction is only slightly 
alkaline, a drug-effect may fail entirely or occur in only a 
slight degree, or, when an opposite condition prevails, so 
large a quantity of the drug may be dissolved that a 
modification of the usual curative effect occurs. This 
latter result is now and then observed to follow the use 
of the golden sulphuret of antimony. While, as a rule, 
it produces only a slight expectorant effect, in some cases 
the full action of the antimony is manifested by the occur- 
rence of vomiting, diarrhoea, and weakness of the heart's 
action. This can be due only to the fact that an excess of 
alkali in the intestinesjdissolves the drug. 

Just as great as that of the gastric acid and the intes- 
tinal alkali is the influence exerted by the chloride of 
sodium, which may be present in the body in much more 
variable quantities than the above-mentioned substances. 
If calomel be administered, for example, widely-varying 
effects are produced upon the functions of individual organs, 
according to the quantity of common salt in the body. In 
the cases of patients who have been long kept upon a low 
diet, calomel has almost no effect, because, in consequence 
of the excessive use of food in a liquid form, the greater part 
of the chloride of sodium has been already washed out of 
the body. On the other hand, as Mialhe asserts, persons 
who have long lived upon a salty diet, as sailors, are 
peculiarly sensitive to the action of calomel, and may pre- 
sent exceedingly intense local irritative effects in the 
intestines, as well as a number of other unpleasant effects 
of mercury. 

From these few briefly-described etiological considera- 
tions, there result numerous possibilities for the occurrence 



14 INCIDENTAL EFFECTS OF DRUGS. 

of perverse drug-effects. In the majority of them, no spe- 
cial constitutional predisposition is requisite. Pathologi- 
cal alterations in the stomach and intestines, as well as 
febrile conditions, which exert an influence upon the com- 
position of the secretions of these organs, or even the in- 
judicious consumption of an article of food capable of 
forming hurtful combinations with certain medicinal 
agents, may predispose to the occurrence of undesirable 
incidental effects. 

While in this manner alterations may be produced in 
different parts of the body, wherever the conditions 
requisite to the formation of products of decomposition 
are present, certain organs which, at the time of the in- 
troduction of certain drugs, are in a pathological state, 
however trivial, may, for this reason, cause temporarily 
such a condition of the body that either the already 
existing alterations are made worse by the medicine, or 
new pathological symptoms are developed in the same 
organs, which, in all probability, would not otherwise have 
appeared. A few illustrations will make this plain. It is 
well known that iodide of potassium is partially elimi- 
nated by the mucous membrane of the air-passages, and 
that it occasionally causes a slight catarrh of these parts, 
which usually disappears when the use of the drug is discon- 
tinued. If, however, these or other lesions be present 
before the administration of the remedy, there may be 
developed, as has been frequently observed, particularly 
in syphilitic patients with ulcers in the larynx, well- 
marked oedema of the glottis, which may speedily result 
fatally. In like manner, very small quantities of drastic 
cathartics, such as elaterium, gamboge, etc., which, in 
medicinal doses, occasionally cause transitory, almost- 
physiological, irritative effects in the intestines, may, 
when the intestinal mucous membrane is in an abnormal 
condition, produce intense inflammation with its con- 
sequences, such as tenesmus, bloody stools, etc. If the 



INTRODUCTION. 



15 



causal relation between such drug-effects and the pre- 
existing- slight organic changes be not understood, it 
would be easy to erroneously regard the former as a 
spontaneous disease of the affected organ. 

It is scarcely necessary to mention the fact that such 
conditions as menstruation, pregnancy, mental excite- 
ment, intense intellectual effort, and sleeplessness — even 
the physiological conditions of fasting or digestion — are 
also capable of modifying the actions of medicines in dif- 
ferent ways. 

§ 7- 

The third cause of a transitory predisposition to the 
occurrence of unusual drug-effects is found in a dis- 
turbance of regulation. When any cause of disease acts 
upon a part of the body, a disturbance is produced, as 
Schiitz has explained upon the ground of Virchow's teach- 
ing. " This disturbance is, however, not pathological, if 
the regulatory apparatus be in a normal condition. Dan- 
ger appears only when regulation is difficult or impossi- 
ble." The good or bad effects of medicines may also 
depend upon the condition of regulation. The latter is here 
to be regarded as identical with elimination. Thus, calomel, 
in a suitable dose, by means of some action upon the intes- 
tinal canal, causes an evacuation of the bowels. As soon as 
this occurs, the greater part of the drug leaves the body 
with the faeces, under the form of sulphate of mercury. 
But if, for any reason, the cathartic effect does not take 
place, the calomel may remain in the intestines, especially 
the cascum, and, by prolonged contact with the chloride of 
sodium there present, be transformed into corrosive sub- 
limate, and thus produce injurious corrosion with ulcera- 
tion of the mucous membrane. 

If a normal regulation, or, better, a proper performance of 
function on the part of the usual emunctories takes place, 
even directly poisonous substances may be taken into the 



l6 INCIDENTAL EFFECTS OF DRUGS. 

body without deleterious effects, while evidences of poison- 
ing manifest themselves as soon as one or the other avenue 
of escape is closed to the drug. Hermann * has utilized this 
fact to explain the intermittent appearance of the symp- 
toms produced by lead. He advanced the hypothesis, 
" that while lead-cachexia is to be regarded as the effect of 
the distribution of certain quantities of lead throughout 
the body, the other symptoms must have a special cause 
which may disappear in spite of the persistence of lead- 
poisoning." This cause he finds in a temporary increase in 
the quantity of lead in the body, either by means of the in- 
troduction of a fresh supply, or a diminution in elimination. 
He designates the condition of saturnism, in which quan- 
tities of lead constantly pass through the body, because 
elimination equals introduction, as " a condition of com- 
pensation." It will be readily understood from this " that 
any diminution of the amount excreted, in consequence of 
any functional disturbance of the eliminating organs, must 
temporarily increase the quantity of lead in the body, and 
so produce new symptoms of an acute character, for the 
causation of which the usual amount of lead is insuffi- 
cient." This is also the reason why many persons seem 
to possess an immunity against the poisonous effects of 
lead, while others become seriously ill after the intro- 
duction of small quantities into the body. It is not 
even necessary that the channels of elimination should be 
pathologically altered ; for there are conditions comprised 
within physiological limits which cause interference with 
the functions of organs ; e. g, the kidneys. According to 
the temperature of the atmosphere, changes occur in the 
quantity of urine excreted, vicariously with increase or 
diminution of the perspiration. This is, perhaps, the 
reason why the great majority of cases of lead colic occur 
during the hot summer months, when the excretion of 

1 Hermann, Archiv f. Anat. u. Phys., 1867, p. 64, und Lehrbuch der Toxi- 
kologie. Berlin, 1874, p. 205. 



INTRODUCTION. l y 

urine is so much diminished in consequence of the free 
perspiration. 

§8. 

In order to thoroughly understand certain abnormal 
effects of drugs, it is necessary, in addition to what has 
already been advanced, to take into consideration that 
condition known under the name of habituation. 

It is well known that, if psychical impressions in their 
widest range, from the most ardent desire to the most in- 
tense aversion, from the greatest joy to the deepest grief 
operate continuously upon the mind, they gradually lose 
their influence. The person becomes habituated to them, 
and the test of their operation, the subjective manifesta- 
tions which they generally produce, finally cease to show 
themselves. We are justified in believing that in such cases, 
the centres of sensibility gradually lose their energy, in 
consequence of the irritations exercised in such rapid suc- 
cession upon them, and fail to present the usual evidences 
of reaction. A readily comprehended analogy for this 
condition is found in the behavior of muscular tissue to- 
wards the electric current. If a muscle be thrown into 
functional activity by frequent irritation of its nerve, the 
action continually increases until the maximum capacity 
of the muscle is reached, and is then succeeded by a stage 
of exhaustion. This continues as long as the muscle is not 
allowed to rest, or until time is given to cast off into the 
blood the products of decomposition resulting from the 
labor. 

Exactly similar conditions obtain in habituation of the 
system to a number of medicinal agents. Antiquity fur- 
nishes us with instances of habituation to poisons. We are 
told that Mithridates could at last find no poison with 
which to destroy his life, because he had gradually so ac- 
customed himself to the use of all that were then known, 
that he could take them in large doses without injurious 



1 8 INCIDENTAL EFFECTS OF DRUGS. 

effects. Aside from this somewhat doubtful tradition, 
it is well to call attention to the use of very active 
agents, such as alcohol, arsenic, opium, and morphine, as 
practised in our own time bv so many persons. The 
quantity of these substances sometimes taken without ap- 
parent injury, by increasing the dose gradually, often 
amounts to ten or twentv times as much as would certainlv 
prove fatal to a healthy man. Other less active drugs, e. 
g., many belonging to the class of laxatives and diuretics, 
entirely lose their characteristic pharmacological effects 
when too frequently administered. At first the effect may 
be still produced by increasing the dose, but this be- 
comes impossible finally, even though the quantity of the 
drug be still gradually augmented. Such results are 
known, e.g., to be produced by rhubarb, castor oil, the neu- 
tral salts such as the acetate of potash, squill, etc. 

How are we to explain these peculiar facts ? If we sup- 
pose any one of these substances to exert its influence 
upon certain cell-groups in the bodv, a normal effect will 
be produced, e. g., sleep will follow the use of morphia, an 
evacuation from the bowels that of rhubarb. A nerve or 
a muscle becomes incapable of performing its function 
under the continued influence of the electric current, on 
account of the material changes which occur in its sub- 
stance. A similar result is produced by the action upon 
the tissues of the bodv of the above-mentioned drugs. The 
difference between the two influences is only this, that 
while on the one hand restitution to the normal condition 
speedily ensues after the cessation of the electric current, 
either by elimination of the products of decomposition, or 
the furnishing of a sufficient supply of new material, on the 
other hand, after the action of drugs upon organs, a restitu- 
tio ad integrum can only occur when the foreign substance 
is in some manner removed from the affected spot. But as 
the complete elimination of such matters from the body 
usually requires considerable time, each newly introduced 



INTRODUCTION. 



19 



quantity finds some of the old still present, and there- 
fore the affected groups of cells are exposed to a con- 
tinuous stimulating or depressing influence. As they are 
thus deprived of the opportunity for recovery, their func- 
tional capacity is lessened, and a physiological or artificial 
stimulus is therefore no longer able to call forth the 
usual reaction. It is true that after every further increase 
in the quantity of the drug administered, an effect is pro- 
duced, but this condition lasts only until exhaustion of the 
tissues occurs. If the drug be discontinued, complete re- 
covery may take place, and the same parts eventually re- 
act normally to medicines. 

The processes above described furnish some insight into 
the possibility of toleration of certain poisonous substances. 
In consequence of the gradually increased consumption of 
such agents, whole cell-groups, particularly those specially 
affected by the poison, are rendered inactive, still adapted, 
it is true, to passive vegetative processes, but no longer 
capable of a definite independent functional activity. The 
poison acts upon inert tissues, which respond to an exces- 
sive dose in the same manner as do normal tissues to one 
small dose. 

Poisonous effects may also be produced even in one 
habituated to the drug, when it is administered in such 
large quantities that the vegetative sphere of the tissues 
is affected and their integrity endangered. 

This is, however, not the only way in which abnormal 
effects may be produced during the persistent habitual use 
of drugs. It is conceivable, in view of the intimate con- 
nection existing between different tissues or organs in the 
production of the functional manifestations of the body, 
that the suppression or limitation of the activity of certain 
parts will be followed by disturbances in the working of 
such organs as stand in functional connection with them. 
In this manner a permanent affection of the brain and 
spinal cord may be followed by alterations in the periphe- 



2o INCIDENTAL EFFECTS OF DRUGS. 

ral nerves, the function of the heart, etc. For this reason, 
not only a number of more or less intense cerebral symp- 
toms occur in those accustomed to the use of opium, but 
also disturbances in the functions of digestion, respiration, 
etc. If the drug be withheld from the bod) 7 , there appear 
symptoms which manifest themselves as a disturbance of 
the previously existing artificial balance in the functions 
of the individual organs. The most characteristic of these 
is the persistent craving for the forbidden drug, reminding 
one of the hunger which is felt for common salt after long 
abstinence from it. Just as this, an essential constituent 
of the body, must be supplied, so has the drug, from its habit- 
ual use, become an integral element for certain organs, and 
its omission is resented in the same way as would be that 
of any other elementary constituent of the body. 

Many facts essential to the comprehension of abnormal 
drug effects result from the considerations just detailed 
bearing upon habituation. It is plain, e. g., that when the 
central nervous system performs its functions in an abnor- 
mal manner, in consequence of the habitual use of a drug 
which specially affects it, the action of another agent, 
which also possesses a special action upon these organs, 
will be an abnormal one. Either no reaction will occur or 
it will be manifested in a perverse direction. As instances 
the action of opium and chloroform on drunkards, partic- 
ularly in delirium tremens, may be cited. 



As an additional and certainly not an unimportant factor 
in the production of many abnormal effects of drugs, it is 
necessary to consider the time of the day or year, and the 
parts of the earth in which they are administered. Tempo- 
ral and localinfluences, although in generalbut little attention 
is now paid to them, even if they do not alone constitute a 
specific idiosyncrasy in man, contribute largely to its pro- 



INTRODUCTION. 21 

duction. For this reason, as Virchow x says, physicians in 
ancient times considered man in relation to the time in 
which he lived, and devoted special attention to " the 
epidemic constitution." Do we not see that certain mor- 
bid influences exert their action only in certain parts of 
the world, and that at different times the same noxious 
agency acts with different degrees of intensity upon the 
body ? If individuals are affected by such external agencies* 
it is easy to understand that certain drugs in a given case 
may produce manifestations abnormal in kind or degree. 
Careful clinical observation has led to the discovery of 
differences in the action of certain drugs in consequence 
of such influences. Thus Charvet 2 found that the effects 
of opium differed in accordance with the time of day, the 
climate, and the race of the subject. Similar observations 
were often made by physicians in the English colonies. 
According to the experience of Lisfranc, the medicinal 
action of the chloride of barium varies greatly in different 
places, much larger doses being borne in southern than in 
northern climates. 

These facts, whose number might be somewhat in- 
creased, are all the more worthy of consideration on the 
part of physicians because, in this very direction, there 
prevails a wide-spread, although unfounded, scepticism. 
We are convinced that careful observation of certain 
effects of drugs, with regard to these points, would result 
in the discovery of a large number of similar deviations 
from the normal. 

§10. 

In view of the importance which, under given circum- 
stances, may attach to the abnormal or injurious effects of 
drugs, another fact is to be considered, viz., that they may 

1 Virchow, 1. c, Bd. vi., p. 29. 

2 Charvet: Die Wirkungen des Opiums auf die th'erische Oekonomie. Leip- 
zig, 1827. 



22 INCIDENTAL EFFECTS OF DRUGS. 

be due to the quality of the drug used. It certainly hap- 
pens much more frequently than is known, or even sup- 
posed, that the non-occurrence of a desired result, or the 
appearance of an undesirable one, is due to an abnormal 
condition of the drugs or pharmaceutical preparations 
which have been administered. This abnormality may be 
due to various causes ; cither the drugs (and this is 
specially true of vegetable agents) while in the crude con- 
dition were pure but of poor quality, or they were good and 
became bad because kept too long, or they were sold mixed with 
foreign substances, or finally, they may obtain unusual qualities 
in consequence of different methods of preparation. 

It must be remembered that in special cases it is extremely 
difficult, or even impossible, to distinguish physically and 
chemically between good and bad drugs, and that very 
thorough study is necessary in order to enable one to form 
a judgment in this regard, particularly in the case of ani" 
mal and vegetable substances. 

The variation in the quality of drugs may also be due to 
the place of their growth. The different kinds of opium, 
aloes, colocynth, etc., are estimated in trade according to 
their origin, which is generally the best criterion of the 
value of a drug. The differences in the modes of action of 
drugs grown in different places are often very great. 
While, e.g., abundant stools are produced by 0.06 to 0.12 
grams (grs. i.-ij.) of Socotrine aloes, a similar result is rarely 
obtained by a dose five times as large of Muscat or Ara- 
bian aloes. Similar differences are seen in the cases of many 
of our domestic officinal plants. Thus the digitalis which 
grows in mountainous regions far surpasses in activity both 
that which grows in the plains and the cultivated variety* 
From the hemp cultivated by us no such haschish can be 
produced as from that grown in hot countries ; and hemlock, 
which with us contains coniine, is in Scotland destitute of 
this alkaloid. The most diverse factors, character of soil, 
temperature of atmosphere, season of the year, etc., are 



INTRODUCTION. * 23 

instrumental in causing these differences. The influence 
of this last factor, in particular, is shown in many of our 
most active drugs, and has here been definitely determined 
by accurate observation. We know that even the digitalis 
which grows in mountainous regions, the Hartz and Black 
Forest, manifests differences in its pharmacological be- 
havior according to the season in which the leaves are 
gathered, it being most active when in full bloom. This 
is also the case with colchicum. It has here also been de- 
monstrated 1 that the roots and seeds gathered while the 
plants are in blossom are the most active, i. e., contain 
the greatest proportion of colchicin. 

Long preservation causes, in the cases of many drugs, 
even when they were originally active, changes in consti- 
tution, or the formation of new and not uncommonly 
noxious products. This is the result of desiccation and 
the oxidizing influence of the air. If, e. g., in the prepa- 
ration of the extract of hyoscyamus, dry, instead of fresh 
leaves are used, it will contain almost no hyoscyamin, while 
the same quantity of leaves from the fresh plant would fur- 
nish it in appreciable quantity. Secale cornutum loses its 
power if not sufficiently dried and kept closely sealed. Such 
a change is most strikingly manifested in the activity of the 
bark of pomegranate root. While the fresh root possesses 
most reliable anthelmintic powers, the dried no longer 
manifests this action, but only produces vomiting or dis- 
turbs digestion. There can be no doubt but that a more 
careful method of treating and preserving drugs than has 
ever been, or is even now, practised, according to the 
opinion of those specially skilled in such matters, would 
have saved many medicinal agents, particularly of the 
class of vegetables, from the fate of being rejected as 
inert by physicians. 

The influence of the atmosphere causes alterations in 

1 Schroff, Zeitschrift der Wiener Aerzte, Jahrg. 7, Bd. i., 185 1. 



2 4 



INCIDENTAL EFFECTS OF DRUGS. 



many purely vegetable as well as other organic and inor- 
ganic combinations. It is well known that, under certain 
conditions, a number of toxic chlorine products may be 
formed in chloroform. In the opinion of French authors, 
morphia acquires its emetic powers by its partial transfor- 
mation into apomorphia, and it has been proven 1 that 
Fowler's solution loses arsenious acid in the course of time, 
probablv under the influence of organic substances which 
have gained access to it. The acid is reduced, and escapes 
as arseniuretted hydrogen gas. Great loss may be occa- 
sioned in this way. 

A further occasion for the occurrence of abnormal 
effects of drugs is furnished by the fact that they are often 
sold mixed with foreign substances, which may find their 
way into the mixture during the process of dispensing. 
Attention has been called to this fact by an expert 2 who 
has shown that very active substances, such as belladonna 
root, hellebore root, etc., may sometimes be found mixed 
with comparatively inert drugs, although in a small pro- 
portion, and that special attention to this fact and accurate 
knowledge of the subject are necessary to avoid the possi- 
bility of harm. Finally, as regards the purity of drugs, in 
so far as this is dependent upon the method of preparation, 
we know that a number of vegetable alkaloids, aconitine, 
digitaline, etc., as well as other chemical bodies, produce 
therapeutical effects, sometimes undesirable ones, varying 
with the methods employed in their preparations. 

In contrast with the variations in the action of drugs 
above-cited, due to the quality of the remedies employed, 
we must consider certain effects which may be produced 
by unsuitable methods of administration, Thus loss of 
appetite, a feeling of oppression in the stomach, diarrhoea, 
etc., in short the symptoms of a catarrhal condition of the 

1 Bretet, Journ. de Pharm. et Chimie, October, 1879, p. 355. 

2 Mayer, Pharmaceutische Centralhalle, 29th July, 1880. 



INTRODUCTION. 25 

intestines, sometimes manifest themselves after the exhibi- 
tion in the form of powder of substances which cause irri- 
tation of mucous membranes, in consequence of the adhe- 
sion of small particles to the lining membrane of the stom- 
ach and intestines. Such symptoms, e. g., may not rarely 
be traced to the use of tannin in the form of a powder. 
In a similar manner the administration of irritating drugs 
in capsules may give rise to functional disturbances in the 
stomach and intestines. 

§n. 

If a general view be taken of all the influences thus 
far considered, which may be the causes of injurious inci- 
dental effects of drugs, it will be seen from their variety 
how often they may come into play, and how essential a 
knowledge of them is. It is true that, as a rule, no per- 
manent functional ill-effects occur in this manner. There 
are, however, many conditions in which permanent disturb- 
ances, even death, may result. It is evident, with this in 
view, that no slight importance is to be attached to these 
considerations from a forensic standpoint. Foreign and 
domestic literature bearing upon this point furnishes abun- 
dant proof of the truth of this statement. Cases have been 
published in which the unfavorable result of a therapeutic 
measure, undertaken with due consideration of the laws of 
the art, has brought the attending physician into a court of 
justice, although the same procedure may have often been 
resorted to by others. For instance, when, after the injec- 
tion into the rectum of an ordinary dose of a solution of 
carbolic acid, death follows, owing to some individual pe- 
culiarity of the patient, or the patient dies in the beginning 
of the administration of chloroform, although a pure drug 
was used, these events are to be regarded as accidents, for 
which no one can be held responsible. The same remark 
applies to other drugs which, under certain circumstances, 
may produce hurtful effects. Well established cases are on 



2 6 INCIDENTAL EFFECTS OF DRUGS. 

record of death occurring in children after the administra- 
tion of 0.006, even 0.0007 gram (gr. -^ — T ^) of opium. If 
the physician were forced to bear the blame in such cases, 
the administration of such drugs would be attended with 
grave personal danger. The most complete safeguard 
against the occurrence of such accidents seems to consist 
in giving the widest possible publicity to them, in order 
that a greater amount of information regarding them may 
be at our disposal than is at present the case. 

§ 12. 

It remains now to give a general view of the mode of 
occurrence of the most important incidental effects hither- 
to recorded in literature of individual drugs. They may 
be the consequence of a direct or reflex action. In only the 
smallest number of cases is it possible to determine with 
absolute certainty in which of these two ways they have 
been produced, owing partly to the method of application 
of the remedy, and partly to the manner in which it is 
eliminated from the body. Thus, it is possible that irritating 
substances introduced into the stomach may exert an ab- 
normal influence in it or in the intestines, and cause gastro- 
intestinal catarrh, with its results. But, in addition, through 
the local changes in the stomach, there may be exerted a 
reflex action upon the functions of the heart, as is the case, 
e. g., with the preparations of antimony. This does not 
preclude the possibility of the heart's action being directly 
affected by the drug after its absorption. This, in fact, 
sometimes occurs. 

It is also conceivable that reflex pathological condi- 
tions of the skin may follow an irritation set up by a drug 
in the intestines or larger bile-ducts, 1 since it is well known 
that other irritating foreign substances, such as the pro- 
glottides of taeniae or gall-stones may by reflex action cause 

1 Litten: Dermatologische Beobachtungen. Charite Annalen, iv., 1S78, 
p. 194. 



INTRODUCTION. 



27 



changes resembling those of urticaria. In an analogous 
manner, material changes may be produced upon other 
points of application of a drug, such as the subcutaneous 
cellular tissue, the mucous membrane of the eye, the bladder 
or the rectum, and by an action reflected from these, func- 
tional disturbances be set up in other organs, and, finally, 
during the circulation of the substance in the blood, phe- 
nomena may occur which differ widely from the primary 
local and reflex symptoms. The instillation of atropia, 
for instance, may cause conjunctivitis, and this, by a re- 
flex action, produce photophobia. But, if the drug be 
absorbed from the lachrymal ducts, symptoms of general 
poisoning may also appear. However, such a subtle dis- 
crimination between these different kinds of effects is, as 
a rule, impossible. 

With regard to the influence of the manner of elimina- 
tion of remedies in bringing about incidental effects, it 
should be stated that in this way effects may be pro- 
duced on different organs, according to the individuality 
of the patients. We know a number of drugs which are 
never eliminated from the body by any other channels 
than the intestines or kidneys, the former when they are 
taken internally, the latter when administered externally 
or subcutaneously. But there are drugs, e. g, antimony, 
which, when applied externally, are first carried into the 
stomach and intestines, and manifest their action in these 
organs. Finally, those remedies must be mentioned which 
usually leave the body with the urine, but, under the in- 
fluence of any of the abnormal individual conditions de- 
tailed in the preceding paragraphs, may, after their inter- 
nal exhibition, choose the skin as their place of exit, their 
presence in this organ being chemically demonstrable. 
As such, among others, may be mentioned iodide of potas- 
sium, bromide of potassium, and arsenic. Others, e. g., 
iodine, may, after injection, be carried into serous cavities 
and thence into the stomach. 



28 INCIDENTAL EFFECTS OF DRUGS. 

If, as is generally the case, active drugs are used, they 
may produce irritant or depressing effects upon the 
organs by which they are eliminated. 

Attempts to explain such phenomena have been made 
most frequently in the case of pathological changes in the 
skin, following the internal use of certain drugs. To 
attribute such effects to one cause only, as is now and then 
done, is apt to lead to errors. It is certain that they may be 
produced in different ways, and are not exclusively due 
either to direct irritation of the glands of the skin or the 
strata of connective tissue, or, through a reflected action, 
to an alteration in the vessels, or to an influence upon the 
cutaneous nerves. 

It is in all cases the drug, as such, which furnishes the 
efficient cause for the changes in the skin, whether it be 
administered in small or large doses. For it is pecu- 
liarly characteristic of individuality and the specific dis- 
position which it causes that influences of whatever kind 
which ordinarily produce no effect, may manifest them- 
selves by causing in different organs changes varying in 
importance. For this reason, the unfounded hypothe- 
sis, 1 that in certain cases, not the drug itself, but certain 
entirely hypothetical substances formed by it in the blood 
were the cause of the pathological phenomena, must be 
absolutely rejected. 

The form of a given drug-exanthema may be differ- 
ent in different persons, and may also be multiform in one 
individual. The differences here manifested must be re- 
garded as tlje expression of individual peculiarities, or as 
dependent upon the varying structure of the skin in differ- 
ent parts of the body. 

The symptoms produced in the organs of special sense, 
as well as in other parts of the body, after the use of dif- 

1 Behrend, Berliner klin. Wochenschrift, 1879, No. 43. 



TONICS 2 Q 

ferent drugs are discussed at length, as regards their gene- 
sis, in the special part of this work. 

TONICS. 

Ferrum. 

A number of incidental effects may be produced by the 
long-continued use of iron, principally upon the digestive 
tract. One observes, not infrequently, in persons with 
normal digestive powers, after the administration of re- 
duced iron, sulphate of iron and other preparations, and 
even iron waters, a disturbance of digestion, a feeling of 
weight in the epigastrium, and vomiting, especially when 
the remedy is taken upon an empty stomach. Defecation 
is delayed, and the fasces are colored black by sulphate of 
iron. 

In very rare cases, hemorrhages are said to occur from 
mucous membranes. 

More commonly there appears after the use of iron, as 
Trousseau 1 states, in healthy individuals, particularly 
women, an acne, occupying the face, breast, and back, and 
running its course without the occurrence of fever. 

After the prolonged use of this remedy, the teeth are 
blackened by a deposit of sulphate of iron. But for the 
production of this result the development of sulphur- 
etted hydrogen, from carious teeth or decomposing secre- 
tions, is essential. The iron dissolved in the alkaline fluids 
of the mouth is at once precipitated by the gas. Even 
when the teeth are healthy, if articles of food or drink 
containing tannin are taken, the formation of tannate of 
iron (ink) may take place. 

Regarding the external application of the sesquichloride 
of iron as a styptic, it is well to call attention to the fact 
that the pain in the wound which is often caused by it is 

1 Trousseau, Gaz. medic, de Paris, 1843, No. 12. 



30 INCIDENTAL EFFECTS OF DRUGS. 

due to the fact that the preparation used was of a bad 
quality, since no pain is produced if the iron salt contain 
no free hydrochloric acid. If it does, the pain is intense, 
although it soon ceases. What is true of the drug in sub- 
stance applies also to the styptic cotton found in trade. 

In order to make the sesquichloride of iron more easy to 
take, and to disguise the sour, sharp taste, which does not 
disappear even after dilution with water, Hager 1 recom- 
mends that the drug be mixed with glycerin or simple 
syrup, and the mixture diluted with cow's milk shortly 
before taking. He claims that in this way the teeth are 
not affected, and that the taste of the iron is concealed. 

Quinine. 

In explanation of the appearance of injurious incidental 
effects after the use of quinine, the opinion has been 
advanced that they are due to a saturation of the or- 
ganism with the drug. From the very great frequency of 
these accidents, however, it has been established that some- 
times even one small dose is sufficient to produce these 
effects, and that, therefore, a certain susceptibility to the 
production of these particular results of the action of qui- 
nine must exist in those cases in which they appear. It has 
indeed been demonstrated by King 2 upon the basis of an 
observation of this kind, that this individual predisposition 
to the production of injurious effects by a certain drug, as 
in this case by quinine, may be hereditary. 

The most different organs may be influenced in this 
manner by quinine, and give evidence of pathological 
alterations. 

On the part of the central nervous system, there are ob- 
served headache, deafness, general muscular excitability, 
sometimes also chilliness and vertigo, disappearing in the 

1 Hager, Pharmac. Ce.itralhalle, 18S0, No. 46, p. 408. 

2 King, Vierte'.jahrschr. f. Dermat. und Syphilis, 1879, P- 37°- 



TONICS. 



31 



horizontal position. Occasionally there appear precor- 
dial anxiety, fainting, or symptoms of collapse. Condi- 
tions of excitation, delirium, etc., on the other hand, are 
very seldom observed. 

On the part of the circulatory apparatus, the action 
of quinine is manifested by a diminution of the heart's ac- 
tion, pallor of the face, and coldness of the lips and skin. 
These phenomena may appear alone, or be attended by 
one of the affections to be later considered, and may last 
from hours to days. 

The skin of many persons is affected in a peculiar man- 
ner by the internal use of even small doses of quinine. 
The eruptions thus produced are characterized by their 
multiformity. Of importance for the explanation of the 
occurrence of these affections is an observation first made 
by Chevallier, 1 and later by other authors, that workmen 
in quinine factories are exposed, by contact with the drug-, 
to an affection of the skin characterized by the appearance 
of vesicles, pustules, or papules on different parts of the 
body, particularly the hands, arms, and legs. This fact 
goes to prove that when diseases of the skin are caused by 
the medicinal administration of quinine, they are due solely 
to the circumstance that the drug is carried into the skin, 
and by irritating this organ produces lesions varying 
in extent, probably in accordance with the vascular distri- 
bution. Of still greater value for the proof of the correct- 
ness of this view than the observation of Chevallier, is a 
fact experimentally discovered by Munk. 2 When he allow- 
ed a current produced by ten Grove's elements to pass 
through a part of the body, after the electrodes had been 
moistened with a solution of the sulphate of quinine, the 
portions of skin acted upon appeared anaemic, dry and 
depressed, immediately after the interruption of the cur- 

1 Chevallier, Annal. d'Hygiene et de Medec. leg., 1851, T. 68, p. 5. 

2 Munk, Archiv f. Anat. und Physiol., 1873, Heft 5. 



32 



INCIDENTAL EFFECTS OF DRUGS. 



rent. Within the next hour, the same parts became much 
swollen, so that they projected considerably above the 
surrounding skin, without, however, undergoing any 
change in color. The swelling disappeared during the 
course of several hours, and gave place to a hyperasmia 
in which there appeared a large number of extravasations 
of blood no larger than the head of a pin, which remained 
after the hyperaemia had subsided. Quinine could still be 
found in the urine twelve hours after the passage of the 
current. In this case, therefore, in consequence of the 
passage of quinine through the tissues, an erythema, and 
later a purpura-like eruption was produced. 

Further proof of the local origin of a quinine eruption is 
furnished by Delioux de Savignac, 1 who saw " a prurigi- 
nous eruption" follow the application to the skin of a salve 
containing the sulphate of quinine. 

Similar eruptions have also been observed after the in- 
ternal use of quinine. These, according to Grissac, 2 appear 
as : 

i.. Purpura. 

2. Roseola. 

3. Scarlatinous exanthema. 

4. Eczema. 

1. Vepan 3 first observed the petechial form. He reports 
that in the case of a lady suffering from neuralgia, who 
took first 0.1, later 0.15 gram (gr. ij.-iij.) of quinine, spots 
of purpura developed all over the body after two days. 
They disappeared nine days after the suspension of the 
remedy, but again showed themselves when its use was re- 
commenced. In this case, the eruption increased in vio- 
lence and extent with the increase of the dose, and hemor- 



1 Deiioux de Savignac, Article quinine, Diet, encyclop. de Scien. med., 
1874, P- 188. 

2 Grissac: Des eruptions quiniques. Paris, 1876, p. 8. 

3 Vepan, Gazette med. de Strassbourg, 1865. 



INTRODUCTION. 



33 



rhage took place from the gums while it lasted. Gauchet 1 
observed a similar petechial eruption on the person of a 
lady who had previously suffered from haemoptysis after 
taking quinine. The petechias were abundantly scattered 
all over the body, and disappeared on the discontinuance 
of the remedy. 

2. A simple roseola, which, however, differs but slightly 
from the eruption next to be described, has been repeatedly 
observed by DaubceuP in males and females. It made its 
appearance attended with intense itching, usually after a 
number of doses had been taken, in one case even eight 
days after the last dose was taken. It was sometimes con- 
fined to the extremities or trunk, and sometimes spread 
over the whole body, and usually appeared only in the 
form of disseminated patches. 

3. The scarlatiniform erythema was first described by 
English authors. Garraway 3 saw it appear simultaneously 
with oedema of the face. In Hemming's case, 4 it appeared 
after the patient took 0.06 gram (gr. i.) of quinine, was at- 
tended with intense itching, a feeling of oppression in the 
prascordial region, and a coated tongue, and disappeared 
with slow desquamation. Skinner 5 saw it appear on a lady 
after 0.06, even 0.03 gram (gr. i., i^),.with shivering and a 
violent chill. It spread over the whole body, and was fol- 
lowed by desquamation which lasted three months. 

The mixed forms of quinine eruptions, a combination of 
the scarlatiniform erythema and acute eczema in its earliest 
stage, are next to be considered. Such an eruption was 
described by Kobner. 6 An eruption which was mistaken 
for scarlatina, preceded by chills, a feeling of prascordial 

1 Gauchet, Bullet, de Therap., lxxxx., p. 373. 

2 Daubceuf, by Grissac, 1. c, p. 22. 

3 Garraway, Brit. Med. Jour., 1869, ii., p. 388. 

4 Hemming, Eod. loco, p. 533. 

5 Skinner, Eod. loco, 1870, i., p. 103. 

6 Kobner, Berl. klin. Wochenschr., 1877, p. 305. 



34 INCIDENTAL EFFECTS OF DRUGS. 

anxiety, nausea, vomiting, and burning on the skin, ap- 
peared in the case of a lady after taking 0.22 gram (gr. iv.) 
of the sulphate of quinine. When the medicine was again 
administered, the face became slightly bloated, and was 
covered with a uniform dark redness which spread also over 
the scalp, ears, neck, and extremities. A few spots of nor- 
mal skin remained on the arms. The flexor surfaces of 
the lower third of both thighs were normal, while the 
extensor surfaces were the seat of isolated papules, of the 
size of a pea, dark-red in color, becoming pale on pressure. 
The intervening tissue was healthy, and the epidermis 
showed fine wrinkling. Heusinger 1 has communicated a 
somewhat similar observation. A nodular eruption, some- 
what similar to erythema exudativum multiforme, ap- 
peared in the case of a lady after she took only 0.025 gram 
(gr. y 2 ) of quinine, on the eyelids, cheeks, and a portion 
of the forehead, with headache, fever, nausea, a sensation 
of intense burning and marked cedematous swelling. On 
another occasion, there appeared in the same case, after 
0.1 gram (gr. ii.) of quinine, only herpetic vesicles on the 
cheeks. The affection disappeared with branny desquam- 
ation immediately after the use of the drug was aban- 
doned. 

The papules upon an erythematous base may also be 
transformed into vesicles, and the eruption thus present 
more of the appearance of an eczema. In this case, the 
itching may be wanting and the general disturbance be 
but slight. Thus Denk 2 reports the case of a boy, in which, 
after the use of 0.8 gram (gr. xiii.) of quinine in four days, 
an eruption appeared without itching, which extended over 
the whole body, became pale on pressure, was of a scar- 
latinous redness, and presented numerous yellow vesicles 
of pin-head size, most thickly collected on the neck, in the 

1 Heusinger, Berl. klin. Wochenschr., 1877, p. 361. 

2 Denk, Wiener med. Wochenschr., 1880, p. 946. 



TONICS. 



35 



axillae, and over the sternum. The general condition, 
with the exception of a slight elevation of temperature 
in the morning and evening, was not affected. After 
the drug was discontinued, the vesicles began to break and 
dry up. Desquamation occurred in small scales and large 
lamellae. 

4. According to Grissac, the appearance of an acute 
eczema may be still more closely simulated than in the 
cases just cited, if the numerous vesicles burst and form 
thick crusts. Such cases are not found in German litera- 
ture. 

In order to distinguish the ordinary quinine exanthema 
from scarlatina, it is necessary, according to Kobner, to 
observe the course of the temperature and to find quin- 
ine in the urine. Denk adds, as diagnostic points, the 
absence of the tongue of scarlatina and the inflammation 
of the palate and tonsils, the fact that the pulse is too slow 
for the initial stage of scarlet fever, and the sudden appear- 
ance of the scarlet redness upon the skin without premon- 
itory symptoms. The presence of quinine in the urine 
may be demonstrated either by discovering fluorescence in 
this fluid after it has been freed from chloride of sodium 
(by precipitating it with nitrate of silver), or by separating 
the quinine in the form of an iodide by means of a solution 
of iodine (two parts of iodine, one of iodide of potassium, 
and forty of water). The iodide of quinine is dissolved on 
the application of heat. 

More unpleasant than the symptoms already mentioned, 
are the disturbances in the organs of special sense observed 
after the use of quinine. 

We shall first consider the disturbances of vision so care- 
fully described by A. von Graefe. 1 After small doses, pho- 
tophobia, as well as temporary amblyopia, is frequently ob- 
served. Under the continued use of larger doses, however, 

1 Von G^raefe, Arch. f. Ophthalmol., Bd. iii., 2, p. 396. 



36 INCIDENTAL EFFECTS OF DRUGS. 

graver disturbances of function occasionally show them- 
selves, which may persist for a long- time and obstinately 
resist treatment. Thus Graefe studied the case of a man 
who, to cure an intermittent fever, took quinine in increas- 
ing doses to 0.9 gram (gr. xiv.) each, or in all about 30 grams 
(3 viiss.). While the dose was being increased one-third 
daily, weakness of vision appeared in the right eye, followed 
in a few days by complete blindness. The left eye remained 
healthy. Nothing abnormal was revealed by an ophthalmo- 
scopic examination made three months later, but the quan- 
titative appreciation of light had disappeared on the right 
side. As von Graefe regarded a disturbance of the intra- 
cranial circulation as the cause of the affection, blood was 
drawn from the temple by means of Heurteloup's leech. 
Quantitative appreciation of light gradually returned first, 
the motion of the hand could next be appreciated, and after 
some time the eye returned to its normal condition. In 
another case, in which 1.8 gram (gr. xxviii.) of the sulphate 
of quinine was taken daily, also for the cure of intermittent 
fever, and in which bilateral amblyopia of a high degree 
appeared, the full power of vision returned spontaneously 
in the left eye, but the right regained only the power to 
read large print. 

The ear may be functionally affected in the same way as 
the eye, and its disturbances may appear with varying 
intensity either simultaneously with the affection of the 
eye or independently of it. Very frequently, as the mildest 
form of the affection, appearing at the same time as other 
nervous disturbances, only a buzzing or ringing in one or 
both ears is observed ; but later difficulty of hearing, and 
even deafness may also appear. According to Briquet, 1 
these symptoms, in most cases, last only a short time. On 
the other hand, Bailly 2 states that incurable deafness may 
follow the use of quinine. 

1 Briquet : Traite Therapeut. de Quinquina et de ses preparats. Paris, 1853. 

2 Bailly, Gazette med. de Paris, 1850, 9. 



TONICS. 



37 



It must also be mentioned that stomach and intestinal 
catarrhs of different grades of intensity are produced with 
tolerable frequency by the use of quinine. For this rea- 
son, Binz 1 warns against the introduction into the stomachs 
of patients with fever, of quinia salts which are not easily 
dissolved. Quinine in a slightly acid solution is readily 
absorbed, and may be taken for weeks without injury ; but 
qininine in powder or pill form, especially the almost in- 
soluble sulphate, may, on account of the lack of gastric 
acid which probably exists in persons with fever, easily 
produce irritation in the stomach and intestines. 

It has been further observed by Guyochin 2 that, after 
the use of quinine, slight irritation of the kidneys and the 
mucous membranes of the bladder and urethra may occur, 
probably owing to the direct contact of the drug with 
these parts. Faginoli 3 treated a child, who suffered from 
painful micturition, and passed a few drops of blood every 
time it took quinine. Monneret saw a genuine hema- 
turia arise in this manner. Piorry and Briquet also claim, 
in very rare cases, to have observed symptoms of cystitis 
following the use of quinine. 

In the case of Gauchet reported above, we have men- 
tioned a symptom which is very rarely alluded to in 
the literature of quinine, viz., haemoptysis. Simon de 
Ronchard 4 was the first to observe several cases of spit- 
ting of blood after daily doses of quinine of 0.5 gram (gr. 
viij.). The affected persons had healthy lungs and hearts. 
As soon as the drug was discontinued the haemoptysis 
ceased, but blood again made its appearance in the sputa 
when it was again used. How this effect of quinine 



1 Binz, Deutsche Klinik, 46, p. 409. 

2 Guyochin : Absorption, Action physiol. et therapeut. de la Quinine, 
Paris, 1872. 

3 F?.ginoli, by Grissac, 1. c, p. 43. 

4 Simon de Ronchard, Gazette des hopitaux, Janvier, 1861. 



38 



INCIDENTAL EFFECTS OF DRUGS. 



occurs has not yet been explained. It has, however, been 
established by the investigations of Merat that, after the 
internal use of quinine, the drug may be found in the 
bronchial mucus. 

Therapeutic measures are but rarely necessary against 
such symptoms as have been detailed, since they disappear 
spontaneously after the discontinuance of the drug. For 
the relief of the conditions of weakness which have been 
described, symptomatic tonics are to be employed if they 
become excessive. 

To prevent the headaches which so frequently appear, 
Wade 1 recommends hydrobromic acid. Fothergill exper- 
imented with this drug, and was able to confirm its reputed 
efficacy. He prescribed two to twelve grams (fl. 3 ss. 
to fl. 3 iij.) diluted with water, of the acid obtained by pre- 
cipitating a solution of forty-seven parts of bromide of 
potassium in three hundred and fifty parts of water with 
fifty-eight parts of tartaric acid. 

Rapid disappearance of the quinine eruption was noticed 
by Lightfoot 2 to follow the administration of twenty-five 
drops of the tincture of hy oscyamus and sponging the body 
with alkalies. Heusinger (1. c.) had the affected portions 
of skin powdered with wheat-flour. 

Salicylic Acid — Salicylate of Sodium. 

Salicylic acid is to be classed with the drugs which 
most frequently and extensively produce undesired effects. 
Some of this class of symptoms seem to be typical attend- 
ants upon the anti-febrile action of the drug, and therefore 
very frequently follow its use. In this category belong 
certain phenomena, yet to be considered, manifested by 
the central nervous system. 

Other symptoms, such as changes on the skin and dis- 

1 Wade, Ref. Virchow-Hirsch Jahresber., 1876, i., p. 400. 

2 Lightfoot, Brit. Med. Jour., 1870, i., p. 30. 



TONICS. 



39 



turbances of the functions of internal organs, appear but 
seldom, and are probably dependent upon an individual 
predisposition on the part of the affected patient. They 
all have this in common, that they disappear rapidly with- 
out leaving injurious results behind. 

On taking salicylic acid, there is experienced a repulsive 
taste, with burning and itching in the mouth and throat. 
After absorption, as Strieker * first stated, there may oc- 
cur buzzing in the ears, difficulty of hearing, and profuse 
sweating — symptoms which do not contra-indicate the con- 
tinued use of the drug. Still more important nervous 
symptoms have been observed by other authors. Thus, 
Riegel, 2 after doses of four to six grams ( 3 i. to 3 iss.), 
noticed, in addition to the above-mentioned symptoms, 
headache, giddiness, and very temporary delirium, and 
Schuhmacher, 3 in addition to these, observed hallucina- 
tions of visions which caused great anxiety. According to 
Riess, 4 besides this condition of psychical excitation, there 
may appear weakness of vision, as well as specks before the 
eyes. Mtiller 5 observed, on the other hand, after the daily 
use for nine days of fifteen grams ( \ ss.) of salicylate of so- 
dium, in a case of diabetes, a condition of psychical depres- 
sion, with violent headache and mental weakness, and, at the 
same time, peculiar motor disturbances. The patient 
complained of weakness in the legs, uncertainty of motion, 
a paretic inclination of the body to the right side, and also 
that, although his sight was good, he ran against objects 
while walking. The symptoms disappeared within five 
days after the use of the drug was discontinued, and 
reappeared when it was again taken in smaller doses. 

1 Strieker, Berl. klin. Wochenschr, 1876, No. 8. 

2 Riegel, Berl. klin. Wochenschr., 1876, 182. 

3 Schuhmacher, Deutsche med. Wochenschr., 1876, No. 18. 

4 Riess, Berl. klin. Wochenschr., 1875, p. 675. 
5 Muller, Berl. klin. Wochenschr., 1877, p. 29. 



40 



INCIDENTAL EFFECTS OF DRUGS. 



Goltdammer 1 observed conditions of collapse of differ- 
ent degrees several times after small doses, five grams (gr. 
lxxv.), of salicylate of sodium. 

No investigations have as yet been made as to the man- 
ner of occurrence of these symptoms, which bear a certain 
resemblance to those produced by quinine, They are 
probably the expression of the direct action of the drug 
upon certain parts of the brain. 

Among functional disturbances of internal organs, those 
which affect the stomach and intestines are first to be con- 
sidered. There exists an isolated observation of Goltdam- 
mer, who, after the administration of twelve grams ( 3 iij.) 
of salicylic acid to a patient with acute miliary tuberculo- 
sis, found after death a number of deep ulcerations of the 
size of a pea, on the mucous membranes of these organs. 
These he attributed to hemorrhagic erosions, probably 
due to the irritating quality of the drug. 

In opposition to this view, Riegel (1. c.) states that, after 
four to six grams ( 3 i. to 3 iss.) doses of the drug, he could 
never find changes in the mucous membrane of the oeso- 
phagus, stomach or intestines. Nevertheless, cases have 
been reported by different observers, in which, after the 
use of salicylic acid and salicylate of sodium, pain was felt 
in the stomach, with vomiting and diarrhoea. 

It would seem that the drug, under certain circum- 
stances, although rarely, is capable of causing irritation 
of the kidneys. Liirmann 2 reports the occurrence, after 
taking four grams ( 3 i.) of salicylate of sodium, of albumin- 
uria, with oedema of both forearms and legs, which ceased 
when the drug was stopped, and reappeared when it was 
again administered. After larger doses, Miiller (1. c.) also 
witnessed the occurrence of diminution in the amount of 
urine, and albuminuria. 

1 Goltdammer, Berl. klin. Wochenschr., 1876, p. 47, 

2 Liirmann, Berl. klin. Wochenschr., 1876, p. 477. 



TONICS. 4 I 

It still remains to consider the changes in the skin oc- 
casionally observed after the use of salicylate of sodium. 
These generally appear as erythema or urticaria, or in a 
petechial form, and are usually attended with intense 
itching. 

After four grams ( 3 i.) of the drug, Heinlein 1 witnessed, 
in a case of articular rheumatism, the appearance, accom- 
panied by unbearable itching, of a diffuse redness of the left 
half of the face, the lower extremities, and the right side of 
the chest, with slight oedema of both eyelids, the upper lip, 
and the legs as far as the middle of the thighs. All these 
symptoms disappeared within twenty-four hours after the 
discontinuance of the drug. When four grams (3 i.) of the 
salt were again administered, there appeared a diffuse 
erythematous redness, with itching, while the whole ab- 
domen, as well as the lower extremities, became covered 
with wheals seated upon a reddened base. The latter 
disappeared spontaneously after an hour, the other mani- 
festations on the following day. Leube also saw an urti- 
caria appear after four grams (3 i.) of salicylate of sodium. 
Freudenberg 2 saw a petechial eruption in an individual suf- 
fering from marasmus, after five grams (gr. lxxv.) of sali'cy 
late of sodium were taken daily for five days. The pete- 
chias, which were the seat of intense itching, and some of 
which were as large as a half-dollar, were originally seated 
upon the back, but spread on the following day over the 
breast, shoulders, upper arms, hips, and thighs. In the 
course of eight days, the spots became paler, and the epi- 
dermis was cast off in great scales from the affected parts 
After complete recovery, five grams (gr. lxxv.) of salicylic 
acid were administered in capsules, with a similar result. 

Resorcin. 
This drug, but recently introduced into the materia 

1 Heinlein, Aerztl. Intelligenzblatt, April, 1878. 

' 2 Freudenberg, Berl. klin. Wochenschr., 1878, p. 630. 



42 



INCIDENTAL EFFECTS OF DRUGS. 



medica, produces, like other antifebrile remedies, when 
administered in active doses, incidental effects, especially 
upon the central nervous system. Lichtheim 1 and Brie- 
fer 2 have reported observations bearing upon this point. 

If two or three grams (gr. xxx. to xlv.) of resorcin are 
administered in solution or in substance, an effect is mani- 
fested in a very few minutes. There appear giddiness, 
buzzing in the ears, and an increase in the frequency of pulse 
and respiration. The face is reddened and the eyes become 
brilliant, the patients being in a condition resembling in- 
toxication. They are sometimes delirious, and manifest 
hallucinations. Speech is stammering, and slight convul- 
sive tremors appear in the hands. 

Soon after taking the drug, the skin becomes moist, and 
in 15 to 20 minutes profuse sweating occurs. At the same 
time, the temperature of the body falls, and the above- 
described symptoms of excitation diminish in intensity. 
Brieger saw collapse occur in this stage, which so increased 
with the diminution of temperature, that powerful stimu- 
lants had to be frequently employed. The fall in tempera- 
ture lasted only a short time. After two or three hours, 
fever abruptly appeared, with a feeling of coolness or even 
a chill. 

Strychnia. 

Strychnia, even in permissible doses, may produce a 
chain of threatening symptoms, differing only in degree 
from true strychnine poisoning. After 0.005, 0.01 gram 
(gr. yV-^) of strychnine, there may appear nausea, red- 
ness of the eyes, formication, exalted sensibility to external 
impressions, a feeling of weight in the feet, and stiff- 
ness in the limbs. With these symptoms are occasionally 
associated disagreeable tension of certain groups of mus- 

1 Lichtheim, Correspondenzblatt f. schweizer Aerzte, 1880, 14, 15 Juli. 

2 Brieger, Centralbl. f . med. Wissenschaft, 1880, 37. 



TONICS. 43 

cles, and painful erections. Girl 1 several times observed, 
after the repeated internal administration of strychnia, the 
occurrence of periodic spasmodic attacks, reappearing 
during- the course of several weeks, of a tertian type, re- 
sembling an intermittent fever, and ending with sweating. 
After they had ceased, they could be reproduced by 
strychnia. 

Children are specially susceptible to the injurious ef- 
fects of strychnia, and for them it must be prescribed with 
extreme caution. A number of cases have been observed 
of severe, even fatal, poisoning by medicinal doses of the 
drug administered subcutaneously for the relief of diph- 
theritic paralysis. 

A skin affection produced by the internal adminis- 
tration of strychnia has also been described. In the 
case of a woman who took 0.0004 gram (gr. y-^-) of 
the drug, Skinner 2 saw a scarlatinous exanthema, which 
disappeared after it was discontinued. 

Colombo Root. 

The Colombo root, so much prescribed as a bitter and 
astringent, probably contains as its active principle berbe- 
rine and the crystalline bitter substance colombine. As 
shown by an experiment of Kohler 3 upon himself, with an 
infusion of twenty grams to one hundred and twenty 
grams of water, a certain amount of care should be taken in 
the use of this drug. It produced nausea, repeated vomit- 
ing, pain in the epigastrium, and finally unconsciousness 
after the subsidence of which a condition resembling that 
following a debauch remained. All these symptoms had 
disappeared after twenty-four hours. For this reason, it 
seems advisable, until more accurate pharmacological in- 

1 Girl, Buchner's Repertorium, xxi., 2. 

2 Skinner, British Med. Jour., 1870, p. 303. 

3 Kohler: Handbuch d. physiol. Therapeutik, 1876, p. 159. 



4 4 INCIDENTAL EFFECTS OF DRUGS. 

vestigations of this substance are at hand, to prescribe it 
only in small doses, rather than as is now the custom. 
Probably in this way only the bitter principle exerts the 
main action, and in larger doses the alkaloid berberine. 

Lignum Quassde. 
Quassia wood, which is an intense poison to the lower 
insects, produces no functional disturbances when occa- 
sionally taken in -small doses as a stomachic. But when 
taken for a long time or in large doses, it produces digestive 
disturbances in some persons, which may be accompanied 
by oppression in the stomach, nausea, and inclination to 
vomit. Furthermore, according to Wibmer, 1 in children 
and delicate adults, dizziness, headache, and deafness ma)^ 
be produced by large doses. Barbier saw in sensitive wo- 
men involuntary muscular movements follow the use of 
a watery solution of quassia wood. 

Herba Chelidonii. 
Celandine, which was formerly regarded as a specific 
for affections of the liver, exerts an action only when 
freshly gathered. The herb then contains a yellow juice 
which may cause an irritation of the skin with the forma- 
tion of vesicles. Taken internally in small doses, it may 
cause nausea and an inclination to vomit, vomiting or 
diarrhoea, and headache. It is said that, after its external 
use, there sometimes appear papular or vesicular eruptions 
on different parts of the body, especially the face. 

Creasotum. 

After the long-continued internal use of creosote in the 

treatment of diarrhoea, there appear, as Richardson found, 

dryness in the mouth, a burning sensation extending from 

the pharynx to the stomach, a white membraniform coating 

1 Wibmer: Die Wirkungen der Arzneimittel und Gifte. Munich, 1842, Bd. 
iv., p. 380. 



TONICS. 45 

of the tongue, and increased frequency of the pulse. In 
rare cases, vomiting and increased frequency of micturi- 
tion also occur, attended with persistent headache. 

An affection of the skin has also been observed after 
taking creosote. M. Bernard 1 saw in the case of a lady, 
no matter in what form he prescribed the drug, an eruption 
attended with violent itching, which proved to be urticaria. 
It disappeared after stopping the medicine, and reappeared 
when its use was a^ain beg^un. 

After the external application of this drug for caries of 
the teeth, there may appear a stomatitis and swelling of 
the tongue, if it comes in contact with this organ and the 
gums. 

When incidental effects make their appearance during 
the internal use of creosote, it must be at once discontin- 
ued, and if gastric disturbance be present, demulcent 
drinks should be prescribed symptomatically. The local 
affections of the mouth soon disappear spontaneously, or 
yield to an antiphlogistic or astringent treatment. 

Oleum Terebinthin^e. 

The oil of turpentine, obtained by distillation with 
water from turpentine, the resinous juice of several varie- 
ties of fir, used either internally or externally in varying 
doses, produces in some persons a number of undesirable 
incidental effects which, in some cases, may render its 
further use unadvisable. 

After the application of the drug to the uninjured skin, 
erythematous changes, sometimes even vesicular eruptions, 
appear, with a feeling of warmth and itching. They soon 
pass off when the drug is discontinued. Upon the sur- 
faces of wounds the action is very intense and may cause 
extensive inflammation. The vapor of turpentine, also, 
may produce a burning and itching erythema, as proved 

1 M. Bernard, Gazette des hopitaux, 1879, p. 170. 



46 INCIDENTAL EFFECTS OF DRUGS. 

by the employment of turpentine vapor-baths in the treat- 
ment of rheumatism, as recommended by Chevandier. 1 In 
animals, the effect upon the skin is manifested by falling 
of the hair. 

Schlothauer 2 also observed the appearance of intense 
salivation and stomatitis after one application of turpen- 
tine for the cure of scabies. This result of the absorption 
of the drug is in all probability due to a reflex excitation 
of the salivary secretion in consequence of an irritation 
of the buccal mucous membrane by the turpentine elimi- 
nated with the expired air, since the introduction of the 
drug into the mouth also may cause an increase in the 
flow of saliva and redness of the mucous membrane. 

The internal use of the oil of turpentine resorted to, as is 
well known, in a large number of affections, such as neural- 
gias, phosphorus poisoning, and colic from gall-stones, fre- 
quently causes many accidental effects, which may be 
intensified to a dangerous degree. Thus, after small 
doses, one occasionally observes burning in the primas 
viae, the formation of vesicles in the mouth, pains in the 
epigastric region, diarrhoea with colicky pains, and vesical 
tenesmus, leading to the discharge of an increased quan- 
tity of urine usually with an odor of violets, and sometimes 
bloody. With the irritation of the kidneys there may be 
associated redness of the urethral mucous membrane and 
painful erections. 

After the repeated use of medicinal doses of the oil of 
turpentine, an effect upon the central nervous system is 
not unfrequently produced, manifested by headache, gid- 
diness, and a feeling of fulness. Purkinje, 3 who took each 
morning for 3 days 4 grams ( 3 i.) of the oil, became sleepy 
after it, and could keep awake only with difficulty ; capa- 

1 Chevandier, Revue Medico-chirurg., 185 1. 

2 Schlothauer, Medic. Zeitung des Vereins fur Heilkunde, 25 Tuni, 1851. 

2 Purkinje, Ref. in 'Mitscherlich's Lehrb. der Arzneimittellehre, Bd. ii., p. 
251. 



TONICS. 47 

city for thought and power of motion remained intact. 
The occurrence of these symptoms may be partially ex- 
plained, since Rossbach and Fleischmann 1 have shown 
that turpentine possesses the power to diminish the excit- 
ability of the central nervous system. Similar effects, due 
to a general action of the drug, may be produced by the 
extensive external application of the oil of turpentine. 

It is finally to be mentioned that, as after its external 
application, changes in the skin sometimes occur after its 
internal use also. According to Berenguier, 2 after com- 
paratively large doses, there appears a simple scarlatina- 
like erythema, spreading by preference over the face and 
the upper part of the body in irregular patches. Some- 
times there appears upon the reddened surfaces, with 
itching, a large number of small papules, which give to 
the skin an eczematous appearance. In rare cases, a vesic- 
ular eruption is noticed. A number of such cases have 
been reported by Brochin, 3 in which erythema or an 
urticaria-like eruption always showed itself in certain per- 
sons after the administration of turpentine, either in solu- 
tion or in capsules or in a pure state. 

Balsamum Copaiba. 
After the use of balsam of copaiba, generally after the 
first day, seldom after the eighth, certain affections of the 
skin appear in certain persons, usually suddenly. They 
were first described by Montegre (1817). In the majority 
of such cases, only a roseola is observed in the beginning. 
The rose-red irregular spots may, however, be transformed 
into true papules, projecting above the skin. Now and 
then the eruption is papular from the start, but, according 

1 Rossbach and Fleischmann : Pharmak. Untersuchungen aus dem Wurzburg 
Instit., Bd. iii. 

3 Berenguier : Des eruptions provoquees par l'ingestion des medicaments. 
Paris, 1874. 

3 Brochin, Gaz. des hopitaux, 1879, Fev., p. 99. 



48 INCIDENTAL EFFECTS OF DRUGS. 

to Bazin, 1 it differs somewhat from an ordinary febrile 
urticaria. Gubler and Rayer have described miliary and 
scarlatina-like eruptions, and also an eczema, as sometimes 
following the use of copaiba, although very rarely. These 
appear by preference upon the upper and lower extremi- 
ties, especially the backs of the hands, the knees, and around 
the malleoli and upon the breast, and sometimes spread 
over the whole body, and are occasionally attended with 
tolerably high fever. According to Berenguier, 2 the rose- 
ola produced by balsam of copaiba sometimes bears a strik- 
ing resemblance to a papular syphilide, but is distinguished 
from it by its sudden appearance, the presence of itching, 
by its affecting by preference the above-mentioned parts 
of the body, and by a peculiar disagreeable odor of the 
skin, and especially by the fact that it disappears when 
the use of the drug is discontinued. 

The eruption is attended with intense itching. The 
spots or papules are either isolated or collected in groups, 
and in the latter case they may form patches of consider- 
able size. They disappear upon pressure, and return 
when it is removed. If the use of the drug be discontinued 
after the appearance of the eruption, the latter may either 
disappear in i or 2 days, without desquamation, or, in ac- 
cordance with the individuality of the patient, or the 
length of time during which the drug was taken, this may 
require from 1 to 3 weeks. Under continued use of the 
drug, the eruption may be transformed into a more severe 
form, and even involve the subcutaneous tissue. 

With reference to a statement of Hardy 3 who saw a 
pemphigus-like eruption after the use of copaiba, Hebra 4 
calls attention to the fact that the eruption was probably 
not a pemphigus, but only an urticaria, and that the ser- 

1 Bazin : Lecons sur les affections cutanees artif. Paris, 1862, p. 184. 

2 Berenguier, 1. c., p. 22. 

3 Hardy, Gazette des hopitaux, 1869. 

4 Hebra: Hautkrankheiten, i., p. 673. 



tonics. 49 

ous infiltration of the layers of the epidermis, which 
causes the wheals of the latter, need only be present in a 
more intense degree in order to produce a bulla. 

Balsam of copaiba also acts injuriously upon various 
mucous membranes, even in not excessive doses, when long 
used. There is not unfrequently observed loss of appe- 
tite, a feeling of weight in the stomach, nausea and vomit- 
ing, and also, according to Bazin (1. a), hyperasmia of the 
conjunctiva and the pharynx, as well as irritation of the 
kidneys and bladder, sometimes resulting in the produc- 
tion of nephritis and cystitis. 

The manner in which these effects are produced is clear. 
Like other resinous substances, balsam of copaiba pro- 
duces a tolerably intense irritation of mucous membranes, 
probably through the oil of copaiba or the copaibic acid 
which it contains. Elimination takes place through the 
lungs, as well as the kidneys, and therefore the urinary 
passages may be irritated in proportion to the quantity of 
the balsam passing through them. The skin may also 
serve as a point of exit for the drug, and, therefore, this, 
organ or its glands may be the starting-point of inflam- 
matory processes. In how far, in different persons, an 
abnormality in vascular distribution, or a peculiar con- 
dition of the glandular elements of the skin may contri- 
bute to the production of such effects, has not yet been 
determined. The fact is, however, established that> after 
the use of balsam of copaiba, the skin frequently emits 
a peculiar odor, probably due to volatile products of 
decomposition of the drug, and that in such cases the 
curative powers of the drug in gonorrhoea are very 
slight. 

It should be stated that the urine passed during the use 
of balsam of copaiba furnishes a deposit with nitric acid, 
which consists of copaibic acid, and may easily be con- 
founded with albumen. 
4 



EjO INCIDENTAL EFFECTS OF DRUGS. 

Maestri and Pidoux 1 report that large doses of balsam 
of copaiba sometimes cause symptoms of poisoning, such 
as paralyses with convulsions and tetanic symptoms. In 
milder cases, there may appear weakness of the arms and 
the muscles of the face, with diminution of the general 
sensibility. 

CUBEB^E. 

As a rule, incidental effects do not follow the use of 
cubebs. In some persons it produces colicky pains and 
diarrhoea. 

An eruption is usually produced only by large doses, 
and in the cases of young persons. It is characterized 
either as an erythema or more frequently a papular 
eruption, which, as in a case reported by Berenguier (1. a), 
spreads over the face, the trunk, arms, and legs. The 
papules are miliary, but unite in many places to form large 
elevations above the skin. The eruption appears without 
attending symptoms, such as fever, etc., and disappears 
in a few days, after the discontinuance of the drug, with 
slight branny desquamation. 

Aqua Calcis. 

The continued use of lime-water, in consequence of the 
persistent neutralization of the gastric acid, not unfre- 
quently causes disturbances of digestion and loss of appe- 
tite ; vomiting has also been observed to follow its use. 
The excretion of urine is increased by this remedy, 
defecation is usually retarded, and in rare cases diarrhoea 
is produced. 

In order to avoid these evils, it has been proposed to use 
saccharate of lime, in doses of 0.5-1 gram (gr. viij.-xv.), 
in watery solution, instead of lime-water. 

The above remarks are also applicable to the carbonate 
of lime. 

1 Maestri and Pidoux, Ref. Schnvdt's Jahrbucher, Bd. 97, p. 301. 



ASTRINGENTS. 5! 

SODII NlTRAS. 

x\fter the use for some time of large, but still medicinal, 
doses of the nitrate of sodium, Loffler 1 observed certain 
changes in the persons who had taken the drug as an 
experiment. Twice there appeared pain and rumbling in 
the abdomen. Digestion was, as a rule, not at all affected 
by the drug. But, increasing with the quantity of the 
drug consumed, there appeared a feeling of general lassi- 
tude, increased on motion, and lasting several days after 
the discontinuance of the drug, disinclination to bodily and 
mental activity, depression of spirits, a tired feeling after 
the slightest exertion, pains in the muscles and joints, 
particularly in the knees, and a continuous inclination to 
sleep. 

The quantity of urea is increased during the first few 
days of the administration of the drug, but afterwards 
returns to, or even falls below, the normal standard. 

ADSTRINGENTIA. 

Alumen. 

After the frequent use of alum, there are observed in 
some persons gastric symptoms, such as loss of appetite, 
nausea, a tendency to vomit, and diarrhoea. These effects 
are due to a direct irritation of the gastro-intestinal 
mucous membrane by the drug, and are dependent upon 
the degree of fulness of the stomach. For if the alum 
introduced into this organ does not meet with enough al- 
bumen or albuminoid substances to precipitate it, the 
mucous membrane is affected by the drug in a greater or 
lesser degree. 

In the experience of Begin and also of Barbier, the long- 
continued use of small doses of alum sometimes produces 
cough in persons with sensitive bronchial tubes. 

1 Lofflei- in Barth, Toxikologische Untersuchungen des Chilisalpeters. Bonn, 
1879, p. 5. 



52 INCIDENTAL EFFECTS OF DRUGS. 

BlSMUTHI SUBNITRAS. 

Perhaps in the case of no other drug do opinions as to 
its eventual hurtfulness or innocuousness differ so widely 
as in that of subnitrate of bismuth. While Monneret, 1 
among others, assures us that the irritating or even poison- 
ous qualities which have been attributed to this substance 
are only imaginary, that it may be taken by patients to 
the extent of three to six teaspoonfuls daily without any 
inconvenience, and that it can act curatively only in such 
large doses, there is a large number of reliable obser- 
vations which go to prove that subnitrate of bismuth in 
medicinal doses [2 to 4 grams (gr. xxx. to 3 j.) daily], may 
sometimes produce hurtful effects. The attempt has been 
made to explain these contradictory statements, by regard- 
ing the impurity of the preparation used, particularly its 
admixture with lead or arsenic, as the cause of the unde- 
sirable incidental effects. In fact, Carnot, 2 among others, 
in all the specimens of subnitrate of bismuth which he ex- 
amined, found lead in quantities varying from from 1 to 
10 per cent. Riche, 3 on the other hand, found it in a 
much smaller proportion, and states that the quantities of 
this metal discovered by him were too small to cause dis- 
turbances in the organism. In fact, Bouchut 4 regards the 
presence of lead as beneficial, claiming that it is this sub- 
stance which enables the bismuth to exert its curative 
action in diarrhoea. 

The proportion of arsenic found in bismuth is also too 
small to produce the symptoms soon to be detailed. The 
anomalous effects of the agent must, therefore, be ascribed 
to the temporary condition of the individual who reacts 

1 Monneret, Centralzeitung, 1849, 43. 

2 Carnot, Comptes rend, des Seances de l'Academie des sciences, T. lxxxvi., p. 
118, 1878. 

3 Riche, Jour, de Pharm. et Chimie, 1878, 28, p. 147. 

4 Bouchut : Jahresb. iiber Pharmakog. u. Toxikol. von Dragendorff, 1879, p. 
268. 



ASTRINGENTS. 



5. 



abnormally under its use, or to its employment in an im- 
proper manner. 

The condition of the individual may be influential in so 
far as the presence in the stomach of greater quantities of 
acid may cause the formation in large quantities, from the 
subnitrate of bismuth, of the corrosive neutral salt, or, if 
this be decomposed by water, of the acid salt. These are, 
however, as Orfila 1 proved by experiments on animals, 
intense poisons, producing gastro-enteritis. The same 
changes would take place if the basic salt were adminis- 
tered at the same time with acid remedies, or if the patient 
should take acid substances after the salt. In this manner, 
the readily soluble nitrate of bismuth, which would be 
formed in the stomach, would be absorbed. 

The incidental effects observed after the use of subni- 
trate of bismuth are almost identical with the pathological 
phenomena which are characteristic of the action of the 
acid salt, and affect principally the stomach and intes- 
tines. Odier 2 saw nausea after its use, Werneck 3 vom- 
iting, colicky pains, and, in some cases, diarrhoea, in 
others, obstinate constipation. With these local symptoms 
were associated a feeling of heat, headache, dizziness, and 
general lassitude. It is especially worthy of remark that 
the stools, after the use of subnitrate of bismuth, are gen- 
erally of a grayish-black color, and almost odorless. This 
is due to the fact that the bismuth salt is transformed 
in the intestine, under the influence of sulphuretted hydro- 
gen gas, into the sulphate of bismuth, and the gas is thus 
held fast. 

The therapeutical indications against the above-men- 
tioned incidental effects are the discontinuance of the 
drug, and the occasional employment of calcined mag- 
nesia in small doses, or of milk, emulsions, etc. 

1 Orfila : Toxikologie, ubers. v. Krupp, 1854, ii., p. 9. 

2 Odier, Jour, de Medecine, 1768, T. 68, p. 49. 

3 Werneck by Wibmer: Wirkungen d. Arzneimittel, T. 1, p. 418. 



54 INCIDENTAL EFFECTS OF DRUGS. 

ACIDUM BORACICUM. 

According to the investigations of Binswanger, 1 boracic 
acid in medicinal doses exerts no action in the human 
organism. If the dose be increased to two or four grams 
(grs. xxx.-lx.), there may occur frequent desire to mictu- 
rate, and an increase in the quantity of urine. In one 
case, after six grams ( 3 iss.) daily, forty-five minutes after 
taking the second dose, nausea and vomiting occurred. 

No incidental effects have as yet been observed after the 
external application of boracic acid. 

Argenti Nitras. 

The changes which silver produces by its long-contin- 
ued external or internal use, consist in a discoloration of 
the tissues in consequence of a deposition of the metal in 
them. Secondarily, as an effect of the presence of this 
foreign substance, functional disturbances may be devel- 
oped in different organs. 

The alterations in the tissues have been frequently made 
the subject of microscopical investigations. Virchow a 
examined a portion of the conjunctiva of a man for whom 
a solution of nitrate of silver had been prescribed as an 
application to the eye, Avhich he had, by mistake, used 
continuously for four months. The conjunctiva presented 
an intense bluish, almost black appearance. A deposition 
of the silver in its substance had taken place, " in such a 
manner, that on the surface the connective tissue was of a 
light brownish-yellow color, and in the deeper portions, 
the deposit had occurred only in the fine elastic fibres or 
corpuscles of the connective tissue." The basis-, or inter- 
cellular substance itself, was normal. 

That the healthy skin may also be the point of entrance 

1 Binswanger : Pharmakolog. Wirkungen der Borsaure und des Borax,. 
Miinchen, 1847. 
2 Virchow: Cellularpathologie, 1871, p. 250. 



ASTRINGENTS. 55 

of the silver is proved by the case ol a woman reported by 
Gamberini. 1 This person, in order to dye her hair black, 
rubbed it every two weeks, for a period of two and a half 
years, with a pomade containing nitrate of silver. She 
afterwards suffered from dyspnoea, palpitation of the heart, 
ascites, and oedema of the legs, after the disappearance of 
which last symptom, the skin became of a slaty-gray or 
light-brown color. 

The recommendation of nitrate of silver for the treat- 
ment of epilepsy, tabes dorsalis, and similar diseases, has, 
in consequence of the chronicity of these affections, led to 
the long-continued use of the drug, and this has frequently 
produced that condition of deposition of silver in the 
tissues known as arguria, with its consequences. It is 
stated that thirty grams ( 3 viiss.) is the smallest quantity 
of silver which has been known to produce this condition. 
The discoloration may affect the whole cutaneous surface 
equally, or be most intense in certain parts, as the face. 
Scars, nails, and hair may also experience changes in 
color. 

Functional disturbances are frequently manifested only 
in the form of gastritis, but in many cases they are entirely 
lacking. 

From the irritation which the drug excites upon the 
mucous membrane of the cheeks, when long used, there 
may result, as Guipon 1 once observed, a stomatitis with- 
out salivation. In this case, the gums were of a dark-red 
color and swollen, and showed a violet border along their 
edges. The incisor teeth were of a slate color, and the 
buccal mucous membrane exceedingly sensitive, particu- 
larly to heat. More recently this affection has also been 
observed by Magitot, 3 and described as "gingivite argen- 

1 Gamberini, Jour, de Medecine, Decembre, i860. 

2 Guipon, Bullet, de Therapeutique, 1866, vo 1 . 71, p 86. 

3 Magitot, Gazette des Hopitaux, 1879, p. 165. 



56 INCIDENTAL EFFECTS OF DRUGS. 

tique." He calls attention to the fact that Charcot saw a 
papular eruption appear upon the skin after the long-con- 
tinued internal use of nitrate of silver, and states that 
both affections are to be regarded as local irritative effects 
produced by silver. 

After the occurrence of arguria, the individual organs 
manifest the following changes : 

Neumann, 1 on examining the skin, found the silver most 
abundant in the papillary layer. A few granules were 
also found in the other layers of the skin, most plentiful 
on the external wall of the hair-follicles, sebaceous glands, 
and sweat-tubes. The epithelial elements, the rete Mal- 
pighii, and the lining of the root-sheaths were free. 

In the case of a man who had taken nitrate of silver in 
large doses for epilepsy, Frommann 2 found, post-mortem, 
an ulcer between the pyloric and cardiac orifices of the 
stomach. The duodenum and jejunum looked as if numer- 
ous little black granules had been scattered over them. 
These, most thickly crowded together along the tops of 
the folds, presented the appearance of a dark, striped pig- 
mentation of the mucous membrane. In the duodenum 
they formed round spots, about one-half of an inch in 
diameter, darkest in the centre, and lighter in color 
around their edges. The intestinal villi contained groups 
of intensely black bodies, which were readily soluble in 
cyanide of potassium. 

Riemer, 3 in the case of a man with tabes dorsalis, who in 
one year had taken five thousand six hundred and seventy- 
two pills containing 34.032 grams ( 3 viiiss.) of nitrate of 
silver, found the surface of the kidneys gray, with numerous 
dark spots corresponding to the Malpighian bodies, and 
the mucous membrane of the pelvis grayish-blue in spots. 



1 Neumann, Sitzungsberichte d. Gesellschaft Wiener Aerzte, 1 Marz, 1878. 

2 Frommann, Virchow's Archiv, Bd. xvii. 

3 Riemer, Archiv d. Heilkunde, 1876, xvi., p. 296 u. 385. 



ASTRINGENTS. 57 

Virchow (1. c.) described the changes in the parenchyma 
of the kidneys produced by arguria, as he found them in 
a preparation in the collection of the Berlin Pathological 
Institute. In this, there is seen in the Malphigian bodies, 
where the transudation of fluid occurs, a blackish-blue dis- 
coloration of the walls of the vessels, limited to this point, 
and in a lesser degree to the connective tissue between 
the straight tubes. Therefore, in the whole kidney, besides 
those parts from which elimination occurs, only those are 
affected which correspond to the ultimate capillary distribu- 
tion in the pyramidal substance. 

In addition to the parts of the body already mentioned, 
silver has been found by Riemer and others in many other 
organs, such as the membranes of the brain, the liver, 
mesentery, walls of the vessels, the heart, etc. 

Opinions differ as to the manner of absorption and depo- 
sition of the metal. Riemer believes that the pigment is 
taken up as such, i. e., in the form of reduced silver, into 
the intestinal canal, is here stored up, and soon carried 
further through the lymphatic glands, being partially de- 
posited on the way, the greater part being carried into 
the current of the blood. Thence it passes through the 
walls of the vessels, being partly deposited in them, the 
remainder becoming permanently fixed in certain portions* 
of the tissues. Riemer, therefore, believes that the cause 
of arguria is dependent upon purely physical laws, as in 
the case of anthracosis pulmonum, and tattooing of the 
skin, in which opinion he is supported by the recent inves- 
tigations of Huet, 1 who found that the particles of silver 
reached the tissues by a sort of diapedesis. Frommann, 
Delioux, and others, on the contrary, believe that silver 
salts can be taken up in the intestinal canal only in a state 
of solution, and they, therefore, claim that arguria occurs 

1 Huet, Journal de l'Anatomie, 1873, p. 10S 



58 INCIDENTAL EFFECTS OF DRUGS. 

in obedience to chemical laws, by precipitation at the 
affected points. 

In the differential diagnosis between arguria and Addi- 
son's disease, the following points are to be considered, 
according to Gamberini. In the latter, the color varies 
between bronze and black, while in the former the skin 
is slaty-gray, with a reddish tinge. When the skin is 
washed with a solution of iodine, an evident change in 
color is produced, which is not the case in Addison's dis- 
ease. 

The treatment of arguria may be directed either to the 
gastric symptoms or to the discoloration of the skin. As 
regards the former, the existing evidences of intestinal 
irritation should be treated symptomatically. In order to 
produce a clearing up of the color of the skin, it is advisa- 
ble, after the successful process of Gamberini, to try the 
internal administration of the iodide of sodium or potas- 
sium, and the long-continued use of warm baths. As 
regards prophylaxis, care must be taken that the silver is 
not used longer than three months, and to the extent of 
at most fifteen grams ( § ss.) 

Plumbi Acetas. 

In view of the recognized poisonous nature of the ace- 
tate, as well as of most of the other preparations of lead, 
and the extensive internal and external employment of the 
agent in relatively large doses, it is remarkable that inju- 
rious incidental effects are not more frequently seen from 
its use than is really the case. Attention must, neverthe- 
less, be directed to the fact that, in the cases of saturnism 
which arise in consequence of the technical use of lead or 
its introduction with the food, the consumption of the 
metal has usually been going on for a relatively much 
longer time than is the case with even the most prolonged 
use of the drug for therapeutic purposes, and that the 
majority of the functional disturbances in the lead disease 



ASTRINGENTS. 59 

are produced by the extremely gradual deposition of mi- 
nute quantities of the metal in the organs and its subsequent 
cumulative action. That there are exceptions to this mode 
of origin of lead poisoning is proved by the fact, particu- 
larly insisted upon by Romberg, 1 that certain persons, who 
are for a long time in contact with preparations of lead, 
nevertheless remain healthy, while others quickly suffer 
from its effects. 

A few cases have been collected by Wibmer, 2 in which 
hurtful incidental effects followed the use of medicinal 
doses of the acetate of lead, probably owing to individual 
causes, such as diminished elimination of the lead by the 
intestines, the kidneys, etc. Baker 3 observed in a man 
who, to cure a hematuria, took for four days, morning and 
evening, 0.06 gram (gr. i.) of the acetate of lead, loss of 
appetite, pain in the stomach, constipation, and paralysis of 
one hand, lasting three weeks. In another case, after the 
use for three days of 0.24 gram (gr. iv.) daily, there oc- 
curred attacks of colic extending over several months. 
Tanquerel des Planches, 4 who was the first to study and 
carefully describe the action of lead, warns against the too 
extensive internal use of its preparations, on the ground 
that it readily produces unpleasant symptoms. 

The external application of lead, in the form of solutions 
and ointments, is also said to be sometimes followed by 
unpleasant results. Those cases in which a discoloration 
of the skin of longer or shorter duration is caused by lead, 
are here first to be mentioned. Foucaud de l'Espagne 5 
reports the case of a lady who, on the order of a physician, 



1 Romberg: Lebrbuch der Nervenkrankheiten, i., p. 167, 

2 Wibmer, 1. c, Bd. iv., p. 23. 

3 Baker, London Med'cal Transactions, i. and ii. 

4 Tanquerel des Planches: Traite des maladies de plomb, ubers. von Franken- 
berg. ii., p. 343. 

5 Foucaud de l'Espagne, Gazette des Hopitaux, 1863, No. 153, p. 611. 



6o INCIDENTAL EFFECTS OF DRUGS. 

used a solution of the acetate of lead as an astringent eye- 
wash. In consequence of the simultaneous use of sulphur 
baths for rheumatism, on the order of another physician, a 
black discoloration of the edges of the eyelids ensued, 
which spread over the cheek-bones and was only removed 
after six days by washing the parts with infusions of aro- 
matic herbs. Berenger-Ferand 1 reports a similar observa- 
tion. In this case, in spite of the use of various acid, alka- 
line, and alcoholic lotions and cosmetics, the black color 
persisted for thirty months. 

The application of solutions of lead upon mucous mem- 
branes and the surfaces of wounds seems in very rare cases 
to produce poisonous effects. Such a case was observed 
by Tanquerel des Planches after the application of lead- 
water compresses to the eye. 

Percival, 2 after the frequent application of the acetate of 
lead as a lotion to a contused shoulder, witnessed the ap- 
pearance of gastric pains, which ceased with the discontin- 
uance of the remedy and reappeared when it was again 
used. The washing of a large ulcer of the leg with lead, 
water, and the application of lead-plaster was followed four 
days later by attacks of colic and paralysis of the extremi- 
ties, which soon passed off after the discontinuance of the 
drug. In another case, observed by Werdermann, after 
the application of lead- water upon an ulcer, there appeared 
a sweetish styptic taste in the mouth and stiffness of the 
neck. In this case also, the symptoms ceased and reap- 
peared in accordance with the abandonment or renewed 
use of the drug. 

From a physiological stand-point, there are no reasons 
for doubting the possibility of the occurrence of such 
effects of lead. Since it has been definitely proved that 
under certain circumstances an absorption of lead into the 

1 Berenger-Ferand, Gazette des Hop., 1864, p. 62. 

2 Percival, on the Poison of Lead, London, 1774, in Wibmer, Bd. vi., p. 237. 



ASTRINGENTS. 6 1 

system may take place even through the normal skin, the 
penetration of lead, particularly the caustic preparations 
which form precipitates with albumen, is comprehensible. 
Of course, only small quantities can be absorbed in this man- 
ner, nevertheless so much may be taken up, that after a few 
applications of the drug it may be demonstrated in the 
urine. The reason why injurious incidental effects so sel- 
dom follow this method of using the drug is unknown. 
Similar individual conditions, however, prevail with the 
majority of drugs, and are not dependent upon the manner 
of absorption. 

ZlNCI OXIDUM. 

The oxide of zinc, as well as all other zinc combinations 
(except the sulphate) which, during the last few decades, 
have been much employed in the treatment of affections 
of the central nervous system, such as epilepsy, eclampsia, 
and chorea, produce, not infrequently, like other metallic 
salts, undesirable incidental effects, pertaining principally to 
the digestive tract. The doses after which they may appear 
range between as low as 0.2 and 0.3 gram (gr. iv.-v.). In 
many persons, there then occur nausea and a feeling of op- 
pression in the epigastrium, differing in degree with the 
individuality of the person, and the amount of food in the 
stomach. For the irritating effect upon the gastric mucous 
membrane becomes 'more intense in proportion as the zinc 
salts have the opportunity, either directly or after their 
solution in the stomach, to form an albuminate by acting 
upon the mucous membrane. If there be sufficient food 
in the stomach to transform all the zinc into an albuminate, 
the irritating quality of the metal is almost entirely neu- 
tralized, since the albuminate goes through the regular 
digestive process, and is then taken up directly into the 
vascular channels. 

In any event, the long-continued use of small doses of 
zinc salts should be avoided, since even with the greatest 



62 INCIDENTAL EFFECTS OF DRUGS. 

care they may produce injurious effects upon different 
functions. Thus Werneck 1 observed in his own case, after 
taking repeated 0.24 gram (gr. iv.) doses of the oxide of 
zinc, oppression in the stomach, eructations, a slight ful- 
ness of the head, later dizziness and a sense of physical 
depression, and after the fourth dose intense thirst, pain in 
the stomach, slight vomiting, and a feeling of tension in 
the limbs. If the zinc salt reaches the intestines and is able 
to irritate the mucous membrane, diarrhoea is also associ- 
ated with these symptoms. Similar effects have been ob- 
served by other authors, even after small doses taken at 
long intervals. It should also be stated that, according to 
Pereira, a zinc dyscrasia, analogous to chronic lead poison- 
ing, may be produced by frequent use of medicinal doses 
of the agent, characterized by obstinate constipation, 
emaciation, and anasmia. 

From a prophylactic stand-point, the symptoms detailed 
above may be easily prevented, if the zinc salt is adminis- 
tered in a soluble form, e. g., as the lactate, and upon a full 
stomach. If, however, the incidental effects have appeared, 
milk and fluid albumen may be given, in order that they 
may combine with any zinc which may be present in the 
stomach. Every effort must also be made to cause its 
speedy elimination from the body, by the administration 
of laxatives and diuretics. 

Cadmii Sulphas. 

The sulphate of cadmium was employed internally by 
Grimaud 2 in the treatment of syphilis, chronic rheumatism, 
etc. It produces, in a still higher degree than the zinc 
salts, irritation of the stomach and intestines, which is, 
however, of a transitory nature. Burdach saw, after 0.06 

1 Werneck, Medic, chirurg, Zeitung, 1831, iii., p. 317 ; ref. in Wibmer, 1. c, 
Bd. v., p. 469. 

2 Grimaud, Gazette medicale de Paris, 1851. 



ASTRINGENTS. 63 

gram (gr. i.), salivation, colic, and frequent stools with 
tenesmus. 

An ointment of the sulphate of cadmium, according to 
Grimaud, produces pustules similar to those caused by an 
ointment of tartar emetic. 

Barii Chloridum. 

The chloride of barium, which on the recommendation 
of Hufeland 1 was formerly employed as a specific in differ- 
ent forms of scrofula, sometimes causes in certain individu- 
als, in quantities less than the maximum, 0.12 (gr. ij.) at a 
dose, 1.5 gram (gr. xxiij.) daily, functional changes in differ- 
ent organs. According to the experience of Lisfranc, 2 the 
medicinal action of this drug is very variable, and much 
larger doses are borne in warm climates than in colder 
regions. 

The disturbances to be noticed on the part of the stomach 
and intestines are nausea and even vomiting, anorexia, 
colicky pains, oppression in the epigastrium and diarrhoea. 
Catarrhal irritation of the conjunctiva, the nasal and respi- 
ratory mucous membranes (that of the last two probably 
extending from the pharynx) have been a few times ob- 
served after the use of baryta. 

After the long-continued use of medicinal doses, the 
symptoms detailed may, as Hufeland also observed, in- 
crease to an excessive degree, even to the production of 
well-marked gastro-enteritis, and with this there may be 
associated symptoms affecting the central nervous system, 
such as giddiness, great anxiety, swooning, muscular weak- 
ness, trembling, and even convulsions. Kohl, 3 in a case in 
which chloride of barium was employed for twenty-four 

1 Hufeland: Ueber die Natur, Kenntniss und Heilart der Scrofelkrankheit, 
P.erlin, 1819. 

2 Lisfranc, by Bernatzik, Encyclopadie der ges. Heilkunde, 1880, Bd. ii , p. 15. 

3 Kohl, in llusemann, Toxicologic, p. 945. 



64 INCIDENTAL EFFECTS OF DRUGS. 

days, observed salivation, swelling of the salivary glands,, 
a bad odor from the mouth, and falling out of the teeth. 

It is not improbable that this intensification of the symp- 
toms produced by the long-continued use of baryta is due 
to a cumulative action of the drug, in consequence of its 
slow elimination with the urine and faeces. This hypothe- 
sis finds support in the fact that, as has been proven, the 
chloride of barium is transformed in the body into the sul- 
phate, and this, an almost insoluble substance, is deposited 
at the point of its origin, and is afterwards gradually cast 
out of the system. In this way it is possible for a more 
intense action of the drug to occur, and one which lasts 
long after its use has been suspended. 

In this manner also, an observation of Schwilgue 1 is ex- 
plained. He found that when he gave small doses of 
baryta, the symptoms of irritation of different organs 
were intensified after the drug was stopped, and lasted 
at least seven weeks longer. 

The treatment of the symptoms detailed consists, in the 
first place, in the suspension of the remedy. The gastric 
disturbances require symptomatic remedies for the relief 
of the inflammation. Diuretics are advisable to cause a 
more rapid elimination of the drug. The use of a direct 
antidote, such as the sulphate of sodium or magnesium, is 
indicated only in very bad cases. 

Acidum Tannicum. 

Individual susceptibility to the action of tannic acid 
varies greatly in different persons. Tully, who took 
daily for a week 0.6 gram (gr. x.) of tannin, experienced 
nothing more than slight nausea and loss of appetite,, 
while Hennig, 2 after even 0.2 gram (gr. iij.), experienced in 
his own case pain in the stomach and intestines, a coated 

1 Schwilgue: Matiere medicale, T. i,. p. 409. 

2 Hennig, Archiv f. physiol. Heilkunde, Bd. xii., 1853. 



ASTRINGENTS. 65 

tongue, eructations, thirst, tenesmus, and an increase of an 
habitual hemorrhoidal congestion. 

After a large dose of tannin, taken for diarrhoea, Roller 1 
observed pains in the stomach and abdomen, obstinate 
vomiting and constipation, lasting fourteen days, besides 
slight febrile movement. After the constipation was re- 
lieved, blood and pus were passed with the fasces. This 
was probably due to a cauterization of the gastric and in- 
testinal mucous membranes by small particles of tannin. 

In order to avoid such unpleasant effects and to still be 
able to take tannin for a long time, L. Lewin 2 recommends 
the administration of the albuminate of tannin, or of tannin 
in an alkaline solution. The former is easily prepared by 
dissolving the desired quantity of tannin in a little water, 
precipitating it by a solution of albumen, and adding albu- 
men in excess to the albuminate of tannin thus formed 
until it is dissolved. For a solution of 2 grams (gr. xxx.) 
of tannin in 100 grams ( 5 iij.) of water, the white of one 
egg dissolved in 100 ccm. ( 3 iij.) of water and filtered, is 
sufficient. Tannin in an alkaline solution may be obtained 
by adding carbonate of sodium to the desired solution of 
tannin until the reaction is slightly alkaline, or by adding 
albumen to it, and again dissolving the tannate of albumen 
by the addition of carbonate of sodium. 

Ergotinum. 

Both the extractum secalis cornuti of Wiggers and that 
of Bonjean produce now and then in medicinal doses (0.2 to 
0.4 gram) (gr. iij. to vij.) a disagreeable taste in the mouth, 
tickling in the throat, increased flow of saliva, nausea, 
burning in the stomach, pains in the abdomen, eructation, 



1 Roller, Wiener med. Wochenschr., 1865, 97. 

2 L. Lewin: Untersuchungen iiber Wirkung und Verhalten des Tannins im 
Thierkorper. Virchow's Archiv, Bd. 81, 1880. 



66 INCIDENTAL EFFECTS OF DRUGS. 

vomiting, and diarrhoea. With some of these symptoms 
there may be associated fulness in the head, headache or 
chilly sensations, giddiness, dilatation of the pupils, and 
general lassitude, unsteadiness of gait, and irregularity of 
the pulse. Aside from the individuality of the patient, the 
differences in the mode of action of the drug are probably 
to be attributed to variations in its chemical composition. 

A number of undesirable incidental effects have also 
been observed after the subcutaneous injection of ergotin, 
first employed by Von Langenbeck 1 (Extr. secal. corn. 
Bonjean, 2.5 (gr. xxxviii.) ; spts. vini, glycefini, aa 7.5 
(gr. cxiii.). This author, after the injection of 0.3 gram 
(gr. v.), noticed the occurrence of specks before the eyes, 
and pain in the shoulder, and Eulenberg 2 saw dizziness 
and vomiting. 

More threatening were the general symptoms which 
appeared in a case reported by Rezek, 3 after the injection 
of 0.04 gram (gr. -§-) of ergotin. Five minutes afterwards, 
the patient made a few convulsive movements with the 
whole body, the pupils became dilated, the eyeballs 
rolled, unconsciousness occurred, the skin became cool, 
and the pulse ceased. Cold douches and the internal 
administration of ether dissipated these symptoms. 

Hildebrandt 4 witnessed milder symptoms. In the case 
of a lady, after six injections, there appeared dizziness, un- 
certainty of motion, spasmodic contractions of the flexors 
of the upper and lower extremities, nausea, and a sense of 
constriction of the chest. As soon as the use of the drug 
was discontinued, these phenomena disappeared, to return 
when it was again employed. 

More common than these general manifestations are the 

1 V. Langenbeck, Berl. klin. Wochenschr., 1869, p. 117. 

2 Eulenberg: Die hypodermat. Injection der Arzneimittel, Berl., 1875, p. 240. 

3 Rezek, ref. by Eulenberg, 1, c, p. 244. 

4 Hildebrandt, Berl. klin. Wochenschr., 1872, p. 298. 



ASTRINGENTS. 6j 

more or less intense local symptoms of reaction. After 
nearly every injection, a painful, nodular infiltration is 
formed at the point of puncture, and in its immediate 
neighborhood, which does not result in suppuration. Hil- 
debrandt, who used injections of ergotin in the treatment 
of fibro-myomata of the uterus, believed that the pain 
caused by the injection of the fluid recommended by Von 
Langeubeck was due to the alcohol which it contains. He, 
therefore, used a solution of Extr. sec. corn, aq., 3.0 (gr. xlv.) 
in glycerine and water, aa 7.5 (gr. cxiii.), and found that it 
caused less pain, but there remained, after the injection, 
persistent, somewhat sensitive, nodules. 

Bengelsdorff, 1 after the injection of ergotin according to 
Hildebrandt's formula (the ergotin in it is not entirely 
dissolved, but a large part suspended), often saw decided 
pain and not infrequently a true phlegmonous, not suppu- 
rative, inflammation spring up more or less extensively 
around the point of injection. At the same time there was 
usually formed a hard nodular swelling, corresponding in 
size to the quantity of fluid injected, which often remained 
eight days or longer. Carrying the canula deep down 
into the tissues and rubbing the skin did not hinder the 
formation of the nodules. 

Folia Salvia. 

The favorite popular remedy, salvia leaves, which are 
occasionally administered internally in the form of an infu- 
sion as an astringent, may, under certain circumstances, 
produce disagreeable effects, as is shown by an experiment 
of Pidoux upon himself, who, after taking a cold infusion 
of the drug, experienced profuse sweating, lasting several 
hours, a bitter taste, and a feeling of dryness in the mouth 
and throat, obstinate constipation, and increased frequency 

1 Bengelsdorff, Berl. klin. Wochenschr, 1874, p. 21. 



68 INCIDENTAL EFFECTS OF DRUGS. 

of pulse. These symptoms represent the combined effects 
of the tannin and the ethereal oil contained in the plant. 

Pix LlQUIDA. 

Tar, which was formerly much used internally in the 
form of tar-water, in the treatment of skin diseases and 
bronchial affections, is now usually employed only exter- 
nally, either pure, as an embrocation for the treatment of 
eczema, or as an inhalation in the form of tar-water. In 
either form it is capable of producing- undesirable delete- 
rious effects, if large quantities of the more active sub- 
stances which it contains are absorbed. 

These effects ma)' be general or local. The general 
manifestations produced by the absorption of small quan- 
tities, are nausea and inclination to vomit, and, after larger 
quantities, headache, a feeling of giddiness, vomiting or 
diarrhoea, associated with abdominal pains. 

The local symptoms are due to an inflammatory irrita- 
tion of the normal, and, in a still greater degree, of the 
morbidly altered skin, probably caused by the carbolic 
acid and creasote, or the empyreumatic substances con- 
tained in the tar. In consequence of this local irritation, 
there is produced, according to Hebra, 1 an acne which 
appears in the form of hard red nodules, and lasts as long 
as the influence of the tar is present. A tar-acne, once de- 
veloped, undergoes involution very slowly, requiring on 
an average a period of two to four weeks for its disappear- 
ance, which occurs, however, without leaving scars or pig- 
mented spots behind. Wilkinson's sulphur and tar oint- 
ment, modified by Hebra (Sulphur, prase, Pic. liquid., aa 
1 80 (|vss.), Cretas, 120 ( 3 iv.), Sapon. vulg., Adipis, aa 
500.0 (O.i.), used for the treatment of scabies, also causes 
eczema, either by being brought in contact with healthy 

1 Hebra: Lehrbuch der Hautkrankheiten, i., p. 594. 



ASTRINGENTS. 69 

parts, or in consequence of the great sensitiveness to oint- 
ments shown by many persons. 

The urine passed after the application of tar often 
shows changes which are probably due to the carbolic 
acid in the tar, and which point to its absorption into the 
blood. Petters 1 found the urine of an intensely blackish- 
brown color, with the characteristic odor of tar. Upon 
distilling it with sulphuric acid, he obtained in the 
distillate carbolic acid and heavy dark-brown oil-drops, 
similar to creasote. For the sake of analogy, it should be 
stated that the dark urine which is occasionally passed 
after treatment with carbolic acid, contains hydroquinone, 
an oxidation-product of carbolic acid. 

Oleum Juniperi Empyreumaticum, or Oleum Cadini. 

The oil of cade, obtained by dry distillation from Juni- 
perus oxycedrus, not infrequently excites inflammatory 
action, when applied to the skin. Kleinhaus, 2 who ap- 
plied the undiluted oil, as is usually done, directly upon 
the surfaces affected with acute, chronic, or impetiginous 
eczema, noticed that even when the skin was but moder- 
ately inflamed, a tolerably intense redness and swelling, 
with acute pain, was developed in consequence of the 
action of the oil, and that soon after the hair-folliclee pro- 
jected above the skin in the form of nodules of the size of 
a hemp-seed — an affection which was seen to be identical 
with tar-acne. 

Bazin observed in patients who used inunctions of the 
oil of cade in the treatment of psoriasis, an eruption of 
isolated or grouped papules, but slightly confluent, hard, 
of considerable size, surrounded by a halo, most plentiful 
on those parts co vered with a well-developed growth of hair. 

1 Petters, Prager Vierteljahrschr , 1855, Jahrg. xii., Bd. 3. 

2 Kleinhaus, Allgem. med. Centralzeit., 1863, No. 24. p. 185. 



jO INCIDENTAL EFFECTS OF DRUGS. 

They were seated upon broad nodular bases, and ended in 
a sharp point, or sometimes a vesicle. A little black point, 
due to the presence of a hair, was always found at the 
summit. These nodules almost never suppurate, and even 
when scratched, only at their apices. The hair-follicles 
are the seat of the affection. Bazin designated it cade- 
sycosis (sycosis cadique). 

In many cases, according to Kleinhaus, the swelling and 
inflammation extend from the original point of application 
over a large extent of surface, and may then present the 
picture of a dermatitis, complicated by erysipelas; in fact, 
even the lymphatic vessels and, through sympathy, the 
lymphatic glands, may participate in the inflammatory 
process. 

In the milder form of the affection first described, hydro- 
pathic applications, with soothing ointments and the dis- 
continuance of the drug, suffice to cause the disappearance 
of the disease. 

To diminish the pain in the wide-spread dermatitic form, 
it is advisable to employ warm baths, in which the patient 
should remain for from one-half an hour to an hour, and to 
give small doses of opium internally. 

An incidental effect of less importance is the brown 
color of the skin produced by oil of cade, which is very 
difficult to remove. In order to avoid this inconvenience, 
the oil may be used in the form of a soap, as Kleinhaus 
did, acccording to this formula: $. Butyr. Cacao, 12.0 
( 3 iij.); 01. Cadini, 9.0 ( 3 ij. gr. xv.); Ol. Lini, Liq. Ammonii 
caust., aa 4.0 ( 3 i.). Of this 5 to 10 grams ( 3 1. to 3 ij.) are 
rubbed in, according to the extent of surface affected. 
This soap can be easily washed off with water. 

ACIDA. 

The dilute inorganic acids, such as sulphuric, hydrochlo- 
ric, phosphoric, and nitric, and the fruit acids, as citric, 



ACIDS. 



71 



tartaric, etc., cause not infrequently, when taken for a long 
period, disturbances of digestion. The appetite dimin- 
ishes, the tongue becomes coated, the teeth ache, and pains 
in the stomach and eructations occur, and sometimes sali- 
vation and diarrhoea. 

After the long-continued use of dilute nitric acid, ac- 
cording to Mitscherlich, 1 the gums and the tongue often 
become ulcerated ; the former bleed readily and the teeth 
are loosened — symptoms which must be regarded as purely 
local effects. 

Acidum Carbolicum. 

The fact that in some persons disturbances of the gen- 
eral nervous system sometimes follow the internal use of 
carbolic acid in medicinal doses has been recognized since 
the first employment of the remedy. Declat 2 observed 
slight headache after its use, lasting from five to fifteen 
minutes, spreading over the whole head, and returning 
every time the drug was taken, most intense in some per- 
sons in the frontal region, in others in the occipital. After 
the administration of the acid in the form of pills, Neu- 
mann observed heaviness and fulness of the head, weakness 
of the legs, dizziness, the appearance of circles before the 
eyes, horripilation, and profuse sweating. 

Only during the past few years has the attention of 
physicians been directed to the exceedingly injurious, 
even fatal, consequences which may, under certain circum- 
stances, follow the external employment of carbolic acid 
in the treatment of wounds. The majority of observers 
believe that in the production of this result the individual- 
ity of the patient is a factor, the nature and power of 
which is unknown to us, but which exerts an immense, if 
not an exclusive influence in bringing about such injuri- 
ous incidental effects. 

1 Mitscherlich: Lehrbuch d. Arzneimittellehre, Bd. iii., p. 81. 

2 Declat: Traite de l'Acide phenique. Paris, 1854. 



72 



INCIDENTAL EFFECTS OF DRUGS. 



Thus Busch l regards carbolic acid as one of the drugs 
which, indeed, act favorably in medicinal doses, but to 
which certain individuals, for reasons as yet unknown, are 
so sensitive that quantities harmless to innumerable other 
persons act poisonously upon them. 

Carbolic acid may gain entrance into the body after any 
method of application. The acid can be detected in the 
tissues, the blood, and the secretions and excretions, as 
well after its application to the healthy skin as to the sur- 
faces of wounds and mucous membranes. In each of these 
methods of application, there may be produced that condi- 
dition described under the name of "carbolism," by which 
we understand an abnormal action of carbolic acid pro- 
duced by one or more medicinal doses. 

It was formerly believed that the most certain criterion 
of the existence of carbolism was the emission of urine 
already brown or greenish when passed, or, if of a lighter 
color then, becoming blackish-brown or deep-brown after 
exposure to the air. Bill believed that the carbolic acid 
was transformed into quinone in the body, and that this 
substance gave the urine its black color. Quite recently 
Baumann and Preusse 2 have given the true explanation 
of this discoloration of the urine. They proved by analy- 
sis of such urine that, in addition to colored products, it 
contained hydroquinone in the form of hydroquinone-sul- 
phuric acid. According to this, a large part of the car- 
bolic acid introduced into the body is transformed into 
hydroquinone by oxidation. One portion of this is 
further oxidized in the system into indefinite colored 
products which pass into and color the urine, while the 
larger part appears in this fluid as hydroquinone-sulphuric 
acid. The dark color seen in many specimens of urine con- 
taining carbolic acid after standing, is due to the fact that 

1 Busch, Berl. klin. Wochenschr., 1880, p. 304. 

2 Baumann and Preusse, Archiv f. Anatomie u. Physiol., 1879, p. 245. 



ACIDS. 73 

the eliminated hydroquinone-sulphuric acid is split up, and 
the hydroquinone thus set free, is oxidized under the influ- 
ence of the air, to form colored compounds. The more 
alkaline the urine, the more rapidly this takes place. 

Careful observations have determined that this carbolic- 
acid urine does not always appear as a pathognomonic 
symptom of the occurrence of noxious incidental effects, 
but that, in a number of cases, it is much rather a series of 
but little characteristic, although dangerous, symptoms 
which make up the picture of carbolism, and may lead to 
a fatal issue. Kuster, 1 who called attention to the poison- 
ous qualities of carbolic acid particularly in the antiseptic 
treatment of wounds, maintained that the reason why so 
few cases of death are recorded in consequence of the 
employment of carbolic acid is, that the majority of them, 
on account of the uncertainty of the symptomatology, are 
concealed under the names of shock, collapse, and similar 
terms. Of five such cases which he observed, four had a 
fatal termination. As predisposing to the occurrence of a 
deleterious action of carbolic acid, he mentions bodily 
weakness and pre-existing diseases. V. Langenbeck 2 saw 
a case of severe carbolic-acid poisoning in the treatment 
with carbolic paste, of abscesses in a boy, and two others, 
ending fatally, after insignificant operations followed by 
the application of the dry dressing. Rose 3 also reported 
a case in which, after the application of carbolized cotton 
which smelt very strong of carbolic acid and was still 
moist, gangrene occurred in a finger which was the seat of 
a wound in full process of healing. 

A striking illustration of the symptomatology of carbol- 
ism is furnished by a well-observed case of Busch (1. c). 
A boy, upon whom an operation for the opening of an 

1 Kuster, Berl. klin. Wochenschr. , No. 48. 

2 Langenbeck, eod. loco, 1878, No. 48. 

3 Rose, Verhandlungen d. Gesellschaft d. Aerzte in Zurich, 19 Dec, 1874. 



74 INCIDENTAL EFFECTS OF DRUGS. 

abscess under the trochanter had been performed, and 
who was exposed to a two-per-cent spray of carbolic acid 
during the few minutes necessary for the operation, and 
afterwards to the action of carbolized gauze, was seized 
on the same day with vomiting, which was attributed to 
the chloroform which had been used. After the dressing 
was opened the next morning under the carbolic spray, an 
inclination to renewed vomiting appeared, and in the 
evening carbolic urine was passed, and later symptoms of 
collapse showed themselves, the pulse becoming small and 
frequent, and the temperature falling to 35. 5 C. (96.5 F.). 
The frequent vomiting made it impossible to introduce 
anything into the stomach, and in spite of the subcuta- 
neous and external employment of analeptics, the patient 
died fifty hours after the operation. 

As an instance of a local organic affection, it may be 
stated that Liicke 1 observed a nephritis due to the action 
of carbolic acid, which disappeared when the use of the 
drug was stopped. E. Wagner 2 studied the changes in the 
kidneys with greater care. Carbolic acid was applied in a 
case of gangrene of the leg. The next day, carbolic acid 
urine was passed, containing casts of medium width, the 
majority hyaline, and a few fatty, some studded with red 
blood-corpuscles or renal epithelium. After death, micro- 
scopic examination showed that the uriniferous tubules 
were dilated, their epithelia large and very fatty, project- 
ing far into their cavities, which contained numerous 
masses of protoplasm and jagged shining bodies. 

In our opinion, not enough importance has been attrib- 
uted to the action of the spray in the discussion of the 
subject of the absorption of carbolic acid during the anti- 
septic treatment. Olshausen 3 believes that the skin is 



1 Liicke, Berl. klin. Wochenschr., 1878, p. 248. 

2 Wagner, Deutsches Archiv f. klin. Medicin, 1880, p. 529 

3 Olshausen, Berl. klin. Wochenschr., 1878, p. 248. 



ACIDS. 75 

rendered much more capable of absorbing the agent under 
the influence of the first dressing, and Langenbuch 1 main- 
tains that absorption by this organ is underestimated in 
comparison with that from wounds, and believes that per- 
haps more is taken up by the normal skin than by the 
surfaces of wounds, during the cleansing process. As 
favoring absorption, he regards the soaping, shaving, and 
scraping of the skin, by which the sweat-glands are opened, 
as well as the literal bathing of the skin by the spray. 

The latter, however, operates in still another manner. 
It has been proved by the investigations of Robrig 2 that 
finely pulverized watery solutions of substances are taken 
up by the skin, while they are not absorbed when simply 
laid upon it. The experiments bearing upon this point, 
which were made with all possible precautions, showed 
that when watery solutions of the iodide or ferrocyanide 
of potassium, e. g., were applied to the skin in a finely 
divided condition, one or the other of these drugs ap- 
peared in the urine. Animals could also be stupefied or 
brought into a paralytic condition by solutions of morphia 
or woorara applied in the same manner. This proves 
that the act of atomizing introduces substances into the 
body much more easily and in larger quantities than sim- 
ple contact. Therefore, the belief is fully justified that a 
very large portion of the carbolic acid employed in the 
spray is absorbed by the skin or its sweat glands. It also 
becomes clear that carbolic-acid poisoning may easily 
occur under these circumstances in the cases of children, 
who naturally possess a much more limited power of 
resistance, since the surface of the skin acted upon by the 
spray is much larger in proportion to the entire surface of 
the body than in adults, and therefore, caeteris paribus, 
much more carbolic acid is taken into the system. Never- 

1 Langenbuch, eod. loc , 1878, p. 414. 

2 Rohrig : Physiologie der Haut, 1878, p. 116, 



j6 INCIDENTAL EFFECTS OF DRUGS. 

theless, the prejudicial influence of soaping, brushing, and 
shaving (manipulations against which Lister has also 
spoken) in facilitating the occurrence of hurtful incidental 
effects, must not be underestimated. 

After what has been said, it will be readily understood 
that the introduction of carbolic acid into cavities lined 
with mucous membrane may also lead to carbolic-acid 
poisoning. The application of enemata containing car- 
bolic acid, and the irrigation of the uterus and vagina 
with this drug, should be considered in this connection. 
Thus Pratorius, 1 in the case of a woman in whom an irri- 
gation of the rectum with a weak carbolic acid solution — 
one-quarter litre (| viij.) of a one-per-cent solution to one- 
third litre ( 3 x.) of warm water — was employed, noticed, 
after a third of this solution had been used, ringing in the 
ears, dizziness, weakness, and fainting fits. Kottmeyer 2 
describes exactly analogous phenomena after the use, per 
enema, of a half-per-cent solution of carbolic acid, in the 
case of a boy suffering from oxyurides. 

Olshausen (1. c.) observed severe symptoms of poisoning 
after washing out the uterus, and Lohlein 3 saw evidences 
of carbolism appear two days after carbolic-acid injections 
into the vagina and uterus of lying-in-women. It must 
finally be mentioned that Edwards, after the introduction 
into the vagina of tampons of cotton impregnated with 
carbolic acid, saw singultus, nausea, chilliness, and ana- 
sarca, with diminution or suppression of urine, delirium, 
and, finally, death. He attributes these phenomena to an 
acute nephritis, with ursemia, produced by carbolic acid. 

The treatment of carbolism should vary with the man- 
ner in which the acid was taken into the body. A directly 
antidotal therapeutic proceeding is generally without re- 

1 Pratorius, Berl. klin. Wochenschr., 1879, p. 214. 

2 Kottmeyer, eod. loc, 1879, p. 501. 
3 Lohlein, eod. loc., 1878, p. 25. 

4 Edwards, Virchow-Hirsch's Jahresber., 1869, 1, p. 349. 



ALTERATIVES. yy 

suit. Husemann and Ummethun recommend the saccharate 
of lime as an antidote, on the ground that lime forms with 
phenol an insoluble compound, but slightly poisonous. 
The sulphate of sodium is also said to act as antidote, by 
combining with phenol, to form the harmless phenol-sul- 
phuric acid. 

If the drug was introduced by enema, it would be well 
to thoroughly wash out the intestine, if only a short time 
have elapsed between the injection and the arrival of the 
physician. In the case of carbolism as ordinarily seen, 
arising from absorption from the skin or from wounds, a 
rapid symptomatic treatment of the general symptoms is 
indicated. The internal or subcutaneous use of stimu- 
lants, energetic irritation of the skin, sinapisms, frictions, 
and the faradic current, will aid in this object. For the 
vomiting, ice-pills and vegetable astringents should be 
administered. 

ALTERATIVES. 

Hydrargyrum. 

Mercury occupies the first place among the remedies 
which, from their extensive therapeutical employment, 
very frequently produce symptoms which cause uneasi- 
ness to the physician, and much more to the patient. The 
affections produced by its external or internal employment 
are of manifold nature. Thev consist both of anatomical 
lesions of the skin and mucous membranes, and of purely 
functional disturbances of various organs without demon- 
strable changes, e. g, of the salivary glands, and also of 
disturbances in the domain of the peripheral and central 
nervous systems. This condition has been described under 
the name of " hydrargyrosis," or " mercurialism." 

In order to obviate the numerous external accidents, as 
well as the directly injurious incidental effects which fre- 
quently occur after the traditional methods of using mer- 



78 INCIDENTAL EFFECT S OF DRUGS. 

cury, several new modes of administration have been 
recommended during the last few decennia, particularly for 
the treatment of syphilis. Inunctions of gray ointment, 
formerly employed in horrible doses — as much as 500 grams 
( 3 xvi.) daily — are well known to still frequently produce 
undesirable results, perhaps for the reason that, while in this 
manner too small a quantity of the drug is taken into the 
body to destroy the syphilitic poison in a short time, the 
mercury absorbed at long intervals, although small in 
amount, is sufficient to act injuriously when the necessary 
predisposition thereto is present. 

The long-continued administration of calomel is also 
sometimes followed by unpleasant results, owing to the fact 
demonstrated by Radziejewski, 1 that when the drug re- 
mains long in the caecum, it is transformed by contact with 
chloride of sodium or ammonium into corrosive sublimate, 
and thus may cause corrosion and ulceration. 

For this reason, the treatment of syphilis with subcuta- 
neous injections of the bichloride of mercury, introduced 
by G. Lewin, 2 in which almost all of the drug is carried 
into the circulation, is to be regarded as an important step 
forward, even although incidental effects are occasionally 
observed to follow the use of the drug in this manner 
also. Quite recently, two other combinations of mercury 
have been recommended for subcutaneous injection by 
Bamberger, 3 with a view to avoid the local irritation often 
produced by corrosive sublimate. One is a solution of 
the albuminate of mercury, prepared from 100 cubic cm. 
( 3 iij.) of a filtered solution of albumen (three to four parts 
of water to one part of albumen), sixty ccm. ( 3 xv.) of a 
five-per-cent solution of corrosive sublimate, sixty ccm. 



1 Radziejewski, Archiv fur Anatomie und F hysiologie, 1870, p. 22. 

2 G. Lewin : Die Behandlung der Syphilis mit Subcutaner Sublimatinjection, 
Berl., 1869. 

3 Bamberger, Wiener med. Wochenschr., 1876, No. 11 and No. 44, p. 1074.' 



ALTERATIVES. yg 

( 3 xv.) of a twenty-per-cent solution of common salt, and 
eighty ccm. ( J iiss.) of distilled water. One ccm. (gtt. 
xv.) of this fluid, which becomes clear after filtration and 
standing for two days, contains o.oi gram (gr. -§-) of the 
bichloride in combination with albumen. 

This solution produces no local irritative effect what- 
ever. This author recommends still more strongly a solu- 
tion of mercurial-peptone, prepared as follows : one gram 
(gr. xv.) of commercial meat-peptone is dissolved in fifty 
grams ( 3 iss.) of water, and the solution filtered. To 
the filtrate, twenty ccm. (3 v.) of a five-per-cent solu- 
tion of the bichloride of mercury is added, and also, in 
order to dissolve the resulting precipitate, fifteen to six- 
teen ccm. ( 3 ss.) of a twenty-per-cent solution of common 
salt. The whole quantity of liquid is diluted with water 
to 100 ccm. (|iij.-), and filtered, after standing for sev- 
eral days. Each ccm. of this solution then contains 0.01 
gram (gr. 1) of mercury, in form of a peptone combina- 
tion. The elimination of the mercury by the kidneys, 
when these fluids are injected, is said to be extremely 
rapid. In any event, great value should be attached to 
the method, since in this manner a cure is much more 
rapidly effected, and the organism is not long exposed to 
the action of mercury. 

We commence the description of the incidental effects 
of mercury with the : 

Changes in the Skin. — The affections of this organ, which 
show themselves in some persons in consequence of the 
use of mercury, appear in the shape of erythemata and 
eczemata (eczema mercuriale). 

The latter was first observed by Benjamin Bell 1 and also 
by Pearson, while Alley' 2 furnished the first exact descrip- 

1 Benjamin Bell: Treatise on Gonorrhoea violenta and Lues venerea, ii., p. 228. 

2 Alley: Observations on the Hydrargyria, or that vesicular disease arising 
from the exhibition of mercury. Dublin, 1804. 



80 INCIDENTAL EFFECTS OF DRUGS. 

tion of this affection, which he called " hydrargyria." 
Hebra 1 and also Kussmaul 2 deny that it possesses any 
characteristic peculiarities as regards its course or symp- 
toms, and therefore regard it as identical with ordinary 
eczema, while Bouchardet considers it a disease sni gen- 
eris. 

According to the statements of older observers, eczema 
mercuriale, which is usually seen only after the external 
employment of mercury, sometimes follows its internal ad- 
ministration also. Thus Alley (1. c.) saw it in an adult after 
taking 0.12 gram (gr. ij.), and in a girl after 0.18 gram 
gr. iij.) of calomel. Ascherson found it in a young man 
after 0.24 gram (gr. iv.). Fournier has recently reported 
a similar case, and Engelmann 3 has cited an instance in 
which, after the use of 0.45 gram (gr. vij.) of calomel in 
0.15 gram (gr. iiss.) doses, there appeared, two hours after 
the last dose, an erythema on the head, attended with febrile 
movement, swelling of the face, etc. The disease spread 
in one night over the whole body, with intense burning 
and itching, and great weakness. Four days later, the 
fever diminished, and the skin began to desquamate on 
the face and breast, partly in large scales, as in the case of 
scarlatina. Appetite and strength returned very slowly. 
The affected person stated that he had frequently suffered 
in the same manner after taking mercury internally. 

In opposition to this view, Hebra denies most positively 
the occurrence of this eruption from the internal use of any 
of the preparations of mercury. In an}' event, its appear- 
ance is extremely rare, and it seems that it can only take 
place under the influence of some individual predisposition. 

On the other hand, this eczema not infrequently follows 



1 Hebra: Hautkrankheiten, i., p. 452. 

2 Kussmaul: Untersuch. uber den constitutionellen Mercurialisums. Wiirzburg, 
1861. 

3 Engelmann, Berl. klin. Wochenschr , 1S79, p. 647. 



ALTERATIVES. 8 1 

the longer or shorter external application of mercury, most 
commonly the inunction of gray ointment. In some 
persons it shows itself after very small doses of mercury, 
and in many others it fails to appear even after the long- 
continued use of large doses. Alley found that twice as 
many men as women suffered from it, which is prob- 
ably due to the fact that men require the use of gray 
ointment much more frequently than women. 

Hebra defines mercurial eczema as a disease of the skin 
which appears in the form of red papules, vesicles, or small 
pustules in great number and closely aggregated. Alley 
distinguishes, according to its intensity and course, three 
forms of the eczema: i. Hydrargyria mitis ; 2. Hydrargy- 
ria febrilis; 3. Hydrargyria maligna. Such a divisionis, 
however, entirely arbitrary, all three forms of the erup- 
tion being essentially the same. 

The exanthema sometimes appears after one, but usually 
after repeated inunction of gray salve, with intense itching 
and burning, usually on the internal surfaces of the thighs, 
the scrotum (or vulva), and in the groins, more rarely on 
the arms, back, and face. In many persons, during the 
whole course of the eruption, there are present febrile 
movement, headache, sleeplessness, and gastric disturb- 
ances. The affected portions of skin are covered with 
dark-red spots readily disappearing on pressure, varying 
in size, and soon running together over a large surface, 
upon which are seated vesicles of pin-head size, and very 
rarely large bullae, with at first clear, later cloudy con- 
tents, which may burst or dry up. ' As a rule, after this 
eruption, which sometimes resembles measles and again 
scarlatina, has lasted for four or five days, the skin becomes 
paler and desquamation begins in large masses or small 
scales. Complete recovery usually takes place in from 
eight to fourteen days. 

In many cases the disease is especially annoying to the 
6 



82 INCIDENTAL EFFECTS OF DRUGS. 

patient, owing to the fact that large portions, sometimes 
the whole, of the body are affected by the eruption ; that 
high fever with angina of the fauces is present, and that 
from the irritating and bad-smelling contents of the nu- 
merous pustules, which burst or are scratched open, and 
which may also undergo relapses, painful excoriations, 
swelling of the skin deprived of epidermis, and the forma- 
tion of crusts may occur. 

In such bad cases of eczema repeated desquamation of 
the epidermis is sometimes observed, and occasionally, 
although rarely, falling out of the hair. This latter occur- 
rence is especially worthy of notice, because in animals 
which have taken mercury for some time, it is the only evi- 
dent effect of the drug upon the skin. 

In addition to these affections of the skin, it is said that 
mercury may, in rare instances, after its external applica- 
tion, cause the formation of gangrenous ulcers, or even 
gangrene. We must, however, agree with Gwalter 1 in 
regarding the existence of such an effect of mercury as 
not proven. 

Nothing positive is known as to the manner of occur- 
rence of the mercurial eruption after inunctions of gray 
salve. Two possibilities are here to be considered, accord- 
ing to either of which it may be supposed that the absorp- 
tions occurs. According to one theory, the preparation 
of mercury, applied by inunction, unfolds its action by 
being vaporized by the heat of the body, and thus gaining 
an entrance into the lungs and the system at large. From 
this point of view, the above-described affections must 
occur secondarily, after the circulation of the drug in the 
organism, and its transformation into corrosive sublimate 
or an oxide of mercury. 

If, however, we adopt the other view, according to 

1 Gwalter: Ein Fall von Quecksilbervergiftung. Inaug. Dissert., Zurich, 
1877. 



ALTERATIVES 83 

which the oleate of mercury, which is constantly being 
formed by rubbing the drug with fat, is absorbed as such 
by the skin, we must suppose that the eruption is due to 
the directly irritating effect of the mercury upon this 
organ. This irritation, if long continued, may lead to a 
hyperaemia of the dermal capillaries, swelling of the epi- 
dermis and sebaceous follicles, and consequently to exu- 
dation and the formation of papules and vesicles. The 
latter is probably the most common, if not the only mode 
of origin of the skin affection. This seems all the more 
probable, because the oleic combinations of mercury may 
exert a corrosive action, like the bichloride, and also 
because when mercurial preparations, even corrosive sub- 
limate, are suddenly introduced into the circulation, e.g., 
by subcutaneous injection, neither erythemata nor ecze- 
mata are ever observed. There, therefore, seems neces- 
sary for the production of the latter affections, a long- 
continued action of a soluble salt of mercury upon large 
portions of the skin, such as is furnished by repeated 
inunctions of gray salve, containing combinations of mer- 
cury with a fatty acid. This, however, does not preclude 
the possibility of the occurrence of skin changes from the 
internal use of mercury, which, in view of recent obser- 
vations on this point, seems likely. 

In opposition to the view held by the so-called anti-mer- 
curialists, concerning the specific character of affections of 
the skin which follow the use of mercury, attention need 
only be called, without entering into subtle deductions, to 
the numerous eruptions mentioned in this work, produced 
by the most heterogeneous substances. These present a 
complete analogy among themselves, and the only specific 
element which they manifest is a direct or reflex action 
upon the skin. 

The treatment of mercurial eczema consists in the imme- 
diate suspension of the drug, and the local application of 
soothing oils, salves, or vaseline. 



34 INCIDENTAL EFFECTS OF DRUGS. 

A second incidental effect of the use of mercury, which 
occurs in about thirty or forty per cent of all cases, is sali- 
vation or stomatitis. Usually only twenty-four or forty- 
eight hours, in rarer cases two or three hours after the 
internal or external use of preparations of mercury in me- 
dicinal doses, there appears either alone or simultaneously 
with redness, swelling, softening, and sensitiveness of the 
gums, or before these symptoms, a sometimes quite exces- 
sive secretion of saliva, even as much as five kilos (eleven 
pounds) in twenty-four hours, which may last all night, 
and prevent the patient from sleeping. It persists usually 
for from three to ten days, or longer, and is attended with 
an offensive odor from the mouth and a subjective 
metallic taste. The saliva itself offers nothing especially 
characteristic. Its specific gravity may rise in the com- 
mencement of the salivation to 1.059, but later falls again. 
After some time it smells bad, has a strongly alkaline reac- 
tion, and irritates the soft parts over which it flows. The 
gums, the mucous membrane of the cheeks and palate, the 
tongue, the soft palate, and also the tonsils, experience 
changes varying in degree according to the individuality 
of the patient, the length of time during which the mer- 
cury was employed, and the amount of the drug used. 
The changes embrace ail stages, from simple hyperaemia 
to the formation of ulcers and necrosis of tissue. 

In the milder grades of mercurial stomatitis, the edges 
of the readily-bleeding gums are covered with a stinking 
yellowish, greasy mass. The teeth may even become 
loose. The ulcers, which are present in the severer forms, 
show a tendency to spread in depth and extent. They 
generally have smooth, jagged edges, and a base covered 
with a thin yellowish secretion. Not infrequently swell- 
ing of the lymphatic glands of the neck is also observed. 

The subjective general disturbances which accompany 
these affections are exceedingly annoying, even in the milder 
forms. The constant flow of saliva causes sleeplessness, in 



ALTERATIVES. 85 

consequence of the necessity of either expectorating or 
swallowing it. To this is added pain, whenever articles 
of food come in contact with the inflamed or ulcerated 
parts. The swelling of the tongue, which frequently 
occurs, interferes with speech, and slight fever, which is 
often present, loss of appetite, headache, and bodily weak- 
ness, render the condition of the patient a very unpleasant 
one. After the affection has lasted for several days, if the 
use of the drug has been meanwhile suspended, the flow 
of saliva becomes less profuse, the changes in the mucous 
membrane of the mouth begin to disappear, and the ulcers 
which may be present, to heal, leaving star-like cicatrices 
behind. If more extensive destruction of tissue be pres- 
ent, many weeks and months elapse before complete re- 
storation occurs. 

The observation has been made that there are two fac- 
tors which predispose to the occurrence of the affection 
of the mouth, and particularly the salivation. These are : 
1, uncleanliness of the mouth ; and 2, a weak anaemic con- 
dition of the body, or previous severe diseases. 

The affections considered above may also be produced 
by subcutaneous injections of mercury. This fact, com- 
bined with the circumstance that mercury may be found 
in the saliva, where it probably exists in an organic com- 
bination, proves among other things that the elimination 
of the metal occurs through the salivary glands, no matter 
what the manner of its use. In this way are explained the 
salivation and the tissue-changes in the mouth, since we 
must believe that, in the first instance, the irritating action 
of the eliminated mercury upon the tissues of the parotid 
or submaxillary gland, or their nerves, must cause, by 
a reflex action, the increased secretion of saliva, and 
that, further, the thus eliminated saliva, which contains 
mercury, if it act long enough, and contain a sufficient 
quantity of the drug, must produce inflammation or ero- 



86 INCIDENTAL EFFECTS OF DRUGS. 

sion of those parts of the buccal cavity with which it 
comes in contact. 

The treatment of a mercurial affection of the mouth 
must, in the first place, be prophylactic. For this purpose, 
patients must attend to cleanliness of the teeth, especially 
removing all products of decomposition contained in cari- 
ous ones. Attention must also be paid to nutrition, in 
view of the predisposition shown by badly nourished indi- 
viduals to the development of such affections. In pro- 
phylactic and curative therapeutics, the first place, after 
the discontinuance of mercury, is still occupied by the 
chlorate of potassium, first recommended by Herpin. 
This acts most safely and speedily upon the affections of the 
mouth. It should be prescribed in a two to three per cent 
solution as a gargle, and also internally to the extent of two 
to three grams (gr. xxx.-xlv.) daily. In cases of pure sali- 
vation, a solution of astringents (sol. Acid. Tannici, 1.0-3.0 : 
150.0) (gr. xv.-xlv. : § iv.) renders good service when 
used for washing the mouth. Besides chlorate of potas- 
sium, alum in one to one and a half per cent solution is also 
used for the same purpose. Sigmund uses tar for paint- 
ing the gums during treatment by inunction, both for the 
prevention of mercurial stomatitis, as well as for curing it 
when already present. Gums which bleed easily, may be 
pencilled to advantage with Tinct. Myrrhas, or equal parts 
of Tinct. Myrrhas and Tinct. Kino, or with Tinct. Rhatanae. 
These last remedies should also be used for the cleansing 
of foul ulcers of the mouth, if it be not preferred to 
employ pure disinfectants, such as carbolic acid (0.5-1 : 150) 
(gr. viij.-xv. : | ivss.) or thymol (0.5 : 500) (gr. viij. : O. i.). 

The incidental effects of mercury hitherto described are 
by far the most common, and occur as well after large 
and medium as after small doses. Although their duration 
is relatively short, they are included in the collection 
of symptoms designated as mercurialism. They only 
prove that the mercury has been absorbed, is circulating 



ALTERATIVES. 87 

through the body, and causing certain functional or ana- 
tomical changes at one of its points of entrance or exit. 
True constitutional mercurialism, however, i. e., the dis- 
turbances of nutrition, sensation, and even motion, which 
seriously affect the animal economy, arises most frequently 
after the loner-continued use of small doses of mercury, 
disappears less speedily, and is probably due to an elimina- 
tion and deposition of the metal in different organs. These 
symptoms are observed in their most pronounced forms in 
workmen who use quicksilver in their occupations, and 
have been described in a classical manner by Kussmaul 
(1. a). They appear more rarely after the medicinal 
employment of mercury, and in the following remarks 
only the positively established facts bearing upon this 
point shall be detailed, without considering the exaggera- 
tions of the enemies of the drug. 

The disturbances of nutrition are always attended with 
alterations of the general condition, and are due almost ex- 
clusively to a direct action of mercury upon the gastro- 
intestinal canal and its secreting glands, and not, as was 
formerly believed, to its mythical faculty of melting the 
organs and drying up the blood. The direct involvement 
of the stomach and intestines is proved by several facts. 
G. Lewin (1. c.) saw, even after the subcutaneous use of 
mercury, especially when the proper doses were exceeded, 
the symptoms of a gastro-enteritis, pain, and burning in 
the region of the stomach, particularly upon pressure, and 
diarrhceic stools, sometimes tinged with blood. In keeping 
with this, the patients felt badly generally ; they were pale, 
and complained of a tired feeling, weakness, and troubled 
sleep. The explanation of this action upon the intestinal 
tract is furnished by the fact that, even after subcutaneous 
injection, mercury is eliminated by this organ. 

In agreement with this stand the changes in the digest- 
ive canal experimentally produced in animals and also 
observed in man, which present the picture of catarrhs of 



88 INCIDENTAL EFFECTS OF DRUGS. 

different degrees of intensity, even of ulceration, par- 
ticularly in the ileum and caecum. In this simple man- 
ner are explained the anorexia, emaciation, vomiting, 
the pains in the stomach and abdomen, and the failure of 
the bodily forces, observed in the cases of many persons 
treated for a long time with small doses of mercury, par- 
ticularly when one considers that the casting-out of the 
drug into the intestinal canal, together w T ith the above- 
described physical anatomical changes in the stomach and 
intestines, destroys the activity of the digestive fluids. In 
such persons there occurs, therefore, in consequence of the 
gradual diminution or loss of appetite, not only a lessened 
assimilation of food, but this process, when the canal is in 
a catarrhal condition, is much retarded, under certain cir- 
cumstances, to such a degree, that, in order to preserve 
the continuity of the nutritive processes, the body is 
forced to live upon itself. 

This view of the matter is well borne out by the result 
of the investigations of the nutritive processes made by V, 
Boeck, in a man who was treated for syphilis by mercurial 
inunctions. He found no changes in the decomposition of 
albumen during treatment. In this case, however, the 
action of the mercury had lasted only sixteen days — a 
period in which the intestinal changes above described do 
not usually appear. It must be especially remembered 
that, for the appearance of disturbances of nutrition, there 
is necessary either a certain predisposition or a prolonged 
action of mercury upon the digestive tract. 

An alteration in the urine which permits us to draw a 
conclusion as to the condition of the kidneys sometimes 
occurs, usually in company with the nutritive disturbances, 
more rarely alone. It not unfrequently contains albumen, 
but in small quantities. Since the kidneys, as has been 
proved, are the organs which eliminate a portion of the 
mercury, the presence of albumen in the urine is most 
probably to be attributed to the irritating action of the 



ALTERATIVES. 89 

drug upon these organs, particularly the uriniferous tu- 
bules. The view that this albumen is not due to an altera- 
tion of the kidneys, but belongs to the metal which is 
eliminated in the form of an albuminate, is proven to be 
unwarranted, by the fact that the urine of persons using 
the drug always contains mercury and but rarely albumen. 
The latter always appears when toxic doses are adminis- 
tered, and then substantial alterations can also be found in 
the urinary passages. In addition to albumen, sugar may 
also be found in the urine after the use of mercury. 
This was. proven by experiments upon animals made by 
Saikowski ' and Rosenbach. 2 In this respect, mercury 
bears a certain analogy to other poisonous substances, 
such as morphia, carbonic oxide, etc. 

The treatment of the general disturbances of nutrition 
consists essentially in a removal of the injurious agent and 
a suitable dietetic regimen. In addition to improving the 
hygienic relations of the patient, the effort must be made, 
by the administration of appropriate non-irritating articles 
of food, to correct any changes which may be present in 
the intestinal canal, and also to cause a rapid and as com- 
plete an elimination of the drug from the body as is possi- 
ble. The latter end may be reached by producing active 
diuresis, by means of vapor and sulphur baths, and espe- 
cially by iodide of potassium, as recommended by Melsens 3 
after the use of which a larger amount of mercury is said 
to leave the body by the kidneys than under ordinary cir- 
cumstances. 

These disturbances of nutrition and the general condi- 
tion, as is also observed in cases of chronic poisoning with 
other metals, are frequently only the forerunners of func- 
tional disturbances of the general nervous system. Occa- 



1 Saikowsk', Virchow's Archiv, p. 346. 

2 Ros-nbach, Zeitschr. f. naturw. Medicin, 3 Reihe, xxxiii., p. 36. 

3 Melsens, Annal. de Physique et de Chimie, III. S., T. 26. 



9<D INCIDENTAL EFFECTS OF DRUGS. 

sionally a few of the latter appear during the course of an 
ordinary treatment by inunction. 

The perceptive disturbances comprise not only an alter- 
ation of certain psychical attributes and feelings, but also 
demonstrable peripheral functional changes in the organs 
of special sense, the touch, sensibility to pain, etc. The 
individuality of the affected person has a great influence in 
this regard, so that in one case a central affection of more 
or less severity is produced as the expression of such a 
disturbance, while in another peripheral ansesthesia or 
hyperesthesia is observed. Among central disturbances, 
the following have been noticed, even after a subcutaneous 
injection of mercury : a condition of psychical erethism, 
appearing at one time as moodiness and increased irritabil- 
ity, at another as terror or timidity, attended with pallor 
of the face, labored asthma-like respiration, and in some 
cases irregular heart-action and great weakness. This was 
first observed by Pearson in persons under treatment by 
inunction, and also by Lewin in a few instances. The 
most pronounced cases were observed by Bauer, 1 and also 
Kussmaul (1. c.) in workmen in mirror-factories. The 
latter regards this form of affection as specially character- 
istic of the action of mercury. If the condition persist 
for some time, there may be developed insomnia, as well 
as other sensorial phenomena, due to increased irritability 
of the brain, particularly the cerebrum, such as hallucina- 
tions and even delirium. These are, however, of a transi- 
tory nature, and must not be regarded as independent 
forms of disease. 

Pains in the joints, the face, and the teeth also fre- 
quently appear, as well as the opposite condition, 
diminution of sensibility, in the form of true anaesthesia 
or analgesia. 

Besides the alterations in the domain of sensation, other 

1 Bauer, Ueber Mercurialismus. Inaug Dissert., Erlangen, i860. 



ALTERATIVES. 9 1 

mercurial affections occur, which manifest themselves as 
motor disturbances. These appear most frequently as 
mercurial tremor, as a rule a chronic affection, but some- 
times occurring- paroxysmally. At first, the hands anijl 
arms are alone affected, as a rule, but gradually, under the 
continued influence of the drug, the legs, as well as the 
muscles of the trunk, experience the same fate. Examina- 
tion of the muscular system, with regard to its electric 
irritability, reveals in such cases a normal condition, de- 
spite the fact that the muscular weakness may be very 
great. In this respect, as well as by the absence of true 
muscular paralysis, the effects of mercury show an impor- 
tant difference from those of lead. 

As a combination of motor and sensory disturbances, 
mention must finally be made of the feeling of giddiness 
which occurs not infrequently, both after the hypodermic 
injection of large doses of mercury and its external 
application. Thus, G. Lewin noticed in some of his cases, 
which had taken large doses of the drug subcutaneously, 
a remarkable weakness, associated with attacks of dizzi- 
ness so powerful that the patients were forced to hold fast 
to surrounding objects in order to avoid falling. These 
vertiginous attacks, attended with a tendency to fainting, 
continued even while the patients lay in bed. The iden- 
tity is complete between these symptoms, appearing after 
one or more large doses of corrosive sublimate, and the 
attacks of dizziness occurring after the long-continued use 
of mercury, which were formerly called mercurial epi- 
lepsy- 

The symptoms pertaining to the central nervous system 
are, without doubt, the consequences of a direct action of 
mercury (called a brain-poison by Kussmaul) upon the 
affected parts, the transitory effects being produced while 
the drug is still circulating with the blood, and the chronic 
in consequence of its deposition in the nerve-centres, and 
the motor and sensory tracts. With regard to the latter, 



9 2 



INCIDENTAL EFFECTS OF DRUGS. 



the investigations of Pickel * should be mentioned. This 
author succeeded in demonstrating, by dry distillation, the 
presence of mercury in the brain of a man who had long 
been treated with the drug. Landerer 2 met with the same 
success in a case of poisoning by corrosive sublimate. To 
what extent mercury becomes permanently deposited in 
the spinal cord and peripheral nerve-distributions has not 
yet been made the subject of investigation. We must, 
however, believe that both the transitory as well as the 
permanent alterations are primarily due to chemical 
changes in the peripheral and central nervous tissues, 
which are perhaps not recognizable by the microscope. 
Histological examination of these tissues, after the use 
of mercury, has, as yet, yielded but insignificant results. 
Pleische found a darker color of the gray substance in 
one case, and Koch of the white in another. 

The prognosis ol these affections, particularly of the 
mercurial tremor, depends upon the length of time during 
which they have existed. It may be favorable when they 
have lasted only a short time, but is doubtful, even if not 
absolutely unfavorable, if the patient has suffered from 
them for a long period. 

The treatment is in the main the same as that of the 
general disturbances of nutrition, and should therefore be 
directed to the removal of the mercurial influence, and as 
complete an elimination as possible of the drug from the 
body. In addition, cold frictions, douches, sea-baths, and 
the simultaneous use of nervines are indicated in conditions 
of erethism also. The electric current should be tried 
for the relief of anaesthesia and analgesia. 

Acidum Arseniosum. 
The similarity of physiological action of the different 

1 Pickel : Buchner's Toxicologic, 1822, p. 433. 

2 Landerer: Buchner's Repertor., III. Reihe, Bd. 25, p. 248. 



ALTERATIVES. g^ 

preparations of arsenic shows itself also in the incidental 
effects which follow the occasional or repeated use of this 
drug, and we shall therefore consider only arsenious acid, 
which may serve as the prototype of all the arsenical pre- 
parations. 

Binz and Schulz 1 have recently shown that if arsenic 
acid is digested for several hours at a temperature of 
38°C. (ioi°F.), with fresh fibrin, brain, white of egg, or 
pancreas, it appears in the dialysate as arsenious acid, and 
after administering arsenious acid to animals, they found 
arsenic acid in the watery contents of the intestines, and, 
vice versa, arsenious acid after giving arsenic acid. These 
processes of oxidation and reduction, according to these 
authorities, take place in the glands, the protoplasma of 
the nerve-centres, and in all other cells in which the condi- 
tions necessary for the occurrence of such actions are 
found. In consequence of this constant transfer of nascent 
oxygen within the molecules of the living albumen, the 
living cells burn more actively than during ordinary tissue- 
changes, and upon this local increased combustion depend 
all the manifestations of the action of arsenic. 

This explanation also facilitates the comprehension of a 
part of the effects, lying outside physiological limits, 
which appear in man after the internal or external use of 
arsenic. 

This applies especially to the effect upon the skin which 
may be produced by the internal or external use of the 
drug in man and animals. This action of arsenic was 
known even to physicians of antiquity. Thus Paulus 
^Egineta' 2 writes: " Arsenici vis est caustica, utuntur eo in 
pilis abolendis, quod si diutius adhaeserit etiam cutem 
ipsam attingit." If arsenious acid in watery solution, or 

1 Binz und Schulz, Archiv f. experimentelle Fathol. u. Pharmakol., Bd. xi., 
p. 200. 

2 Paulus ^gineta : Opera, ed. J. Guinterius, Lugduni, 155 1, p. 479. 



9 4 INCIDENTAL EFFECTS OF DRUGS. 

in the form of a salve or a paste, remains for some time in 
contact with the healthy skin, an inflammatory irritation 
appears, attended with pricking or burning pains and mild 
fever, and vesicles or pustules may form on the reddened 
and swollen surface, without the appearance of systemic 
absorptive effects. If the inflammation increases, an ery- 
sipelatous swelling, and, subsequently, discolored san- 
guinolent eruptions may, according to Falck, 1 mark the 
beginning of general poisonous effects, in the same manner 
in which they follow the internal administration of arsenic, 
as will presently be described. This is also the case if the 
agent is applied to the surface of wounds. The hairs on 
the affected surfaces fall out, as a rule. The eruptions 
heal with exfoliation of the epidermis in large flakes. 

Entirely analogous changes of different kinds in the 
skin have been seen after the internal use of arsenic 
in ordinary medicinal doses, particularly in the form 
of the usually employed Fowler's solution. How va- 
ried these affections may be is seen from the homce- 
opathically-inspired description of Imbert Gourbeyre. 2 
He says : " Eruptions petechiales ou ecchymoses, erup- 
tions papuleuses, ortiees, vesiculeuses, erysipelateuses, 
pustuleuses . . . telles sont les principales formes de l'arsenic 
exanthematogene dans ses manifestations a la peau." In 
accordance with this, different authors describe the arsenic 
eruptions differently. Thus, Macnal 3 reports a rubeola- 
like exanthema in patients who, for three days, had taken 
only c.i 8 gram (gtt. iij.) of Fowler's solution. Pereira, 
in a case of gout, for which he had prescribed o.oi gram 
(gr. -$-) of the arsenite of potassium daily, saw on the third 

1 Falck : Die klinisch wichtigen Intoxicationen, Virchow's Path. u. Therap., 
Bd. i., p. 254. 

2 Imbert-Gourbeyre, Gaz. med. de Paris, 1862, p. 227, and Etude sur quelques 
Symptomes de l'Arsenic. Paris, 1862. 

3 Macnal, Medical Times and Gazette, 186S. 



ALTERATIVES. 



95 



day, after a sleepless night with headache and feeling of 
increased warmth of the skin, an intensely red eruption 
on the face, the neck, the upper part of the body, and the 
flexor surfaces of the joints, with oedema of the eyelids. 
The eruption disappeared between the third and fifth 
days, while the desquamation lasted nearly two months, 
and occurred in large flakes. When, after the disappear- 
ance of all the symptoms, arsenic was again administered, 
the same phenomena again showed themselves, accompa- 
nied with profuse salivation. According to Imbert Gour- 
beyre, the eruption appears by preference on the neck, 
face, and genital organs, and also on the hands. The pa- 
pules, of pin-head size, which compose it, appear at first in 
scattered groups, but unite later and form patches as large 
as a bean and larger. This author, like Pereira, says that 
the eruption lasts for six or eight days, but he saw only 
a branny desquamation of the epidermis after it. 

How small a dose suffices to produce an eruption is 
shown by a case reported by Bazin, 1 in which ecthyma- 
like pustules appeared after the consumption of 0.05 gram 
(gr. -§-) of arsenic during fourteen days. 

In this connection, mention should be made of the state- 
ment of Wyss, 2 that he saw alopecia areata develop on a 
boy after the prolonged internal use of arsenic. He uti- 
lizes this observation to establish the view that this disease 
is due to a disturbance of nutrition of the hair-follicles, 
and not to the presence of a fungus, as recent observers 
seem again inclined to believe. 

If we review the facts here detailed, bearing upon the 
action of arsenic upon the skin, it cannot be denied that 
the changes in this organ, produced by the external and 
internal use of the drug, are identical. After its internal 
administration, therefore, there must occur in certain cases 

1 Bazin: Lecons sur les affections cutanees artificielles. Paris, 1862, p. 196. 

2 Wyss, Archiv f. Heilkunde, Bd. xi., 1870, p. 17. 



g6 ' INCIDENTAL EFFECTS OF DRUGS. 

a penetration of the arsenic into the skin, and a partial eli- 
mination of the drug by this organ. This is in fact the 
case, as is shown by the experiments of various authors. 

Chatin * succeeded in finding arsenic in the contents of a 
bulla produced by cantharides upon the skin of a person 
poisoned with arsenic. 

Barella 2 proved the direct elimination of arsenic by the 
sweat-glands, especially when the skin acts vicariously for 
the kidneys, while Bergeron and Lemattre 3 demonstrated 
that combinations of arsenious acid with alkalies could be 
cast out with the sweat, while, on the other hand, the ar- 
senite of iron is so split up in the body that the iron passes 
into the urine, while the arsenic appears in the sweat in 
the form of arsenite of potassium. 

In view of these facts, we must regard the skin affections 
already described, no matter by what method of adminis- 
tration of the drug they were produced, as due to a direct 
local action of arsenic, and must seek the ultimate reason 
of their occurrence, according to Binz and Schulz, in a 
local increased combustion in the living cells. 

Since the arsenical eruption, as has already been stated, 
disappears spontaneously in a few days, therapeutic inter- 
ference with it is hardly necessary. In cases in which the 
inflammation of the skm has attained serious dimensions, 
or has taken on a malignant character, it will be necessary, 
in addition to furthering the elimination of the poison 
through the kidneys by means of diuretics, to resort to 
local antiphlogistic treatment, and in case products of de- 
composition are present, to proceed antiseptically. 

Much more frequently than the phenomena thus far 
described, there appear after the internal use of arsenic 
for a shorter or longer period, according to the individu- 

1 Chatin, Jour, de Chimie medicale, 1848, p. 328. 

2 Barella, Jour, de Medicine de Bruxelles, Juillet, 1863. 

3 Bergeron and Lemattre, Archiv gener. de Medicine, 1864, Vol. ii., p. 173. 



ALTERATIVES. 



97 



ality of the patient, irritation of the mucous membranes of 
the mouth, throat and stomach, and consequently digestive 
disturbances. The tongue in such cases is thickly coated, 
and there appear an unpleasant burning in the mouth, 
thirst, a feeling of oppression in the stomach, loss of appe- 
tite, eructation and even vomiting. The affection of the 
mouth may assume the character of an angina or stoma- 
titis, and not infrequently free salivation is observed after 
very small doses of arsenic have been taken. Harles 1 first 
discussed this fact in the following words : " Diutius con- 
tinuato arsenici usu satis parco excitatur haud ita raro 
salivas aliquanto largior secretio, sive ptyalismi levior 
species." In modern times, similar statements have been 
made by Imbert-Gourbeyre (1. c.) and Trousseau and Mor- 
ganti, 2 among others. 

This irritation of the buccal mucous membrane spreads 
not infrequently to the air passages, resulting in the pro- 
duction of a dry cough, bronchitis, and harshness of the 
voice. If the nasal mucous membrane be attacked, there 
appear burning in the nose and coryza and (although but 
rarely), as Heim 3 first observed, epistaxis. 

If the tear-ducts and conjunctivae become affected in 
consequence of the extension of the catarrhal process 
(which occurs quite frequently), the patient suffers from a 
flow of tears, photophobia, amblyopia, and sometimes swell- 
ing of the eyelids and the usual symptoms of conjunctivitis* 
the objective included. Very rarely an icteric discolora- 
tion of the sclerotic is Observed — a phenomenon which is 
tolerably common, in connection with xanthopia, in acute 
arsenical poisoning. 

As nervous symptoms there appear in some cases head- 
ache, buzzing in the ears and giddiness. 



1 Harles: De usu arsenici, Norimbergse, 1811, p. 301. 

' 2 Morganti, Gaz. med. de Paris, 1852. 

3 Heim: Vermischte Schriften, 1836, p. 302. 

7 



gS INCIDENTAL EFFECTS OF DRUGS. 

It must finally be mentioned that it has been stated by 
French authors, such as Charcot 1 and Devergie, 2 that ana- 
phrodisia not seldom follows the use of Fowler's solution. 
This diminution of the sexual instinct disappears after the 
discontinuance of the drug. 

The treatment of the symptoms described consists in the 
immediate withdrawal of the drug and the use of demul- 
cents for the affected mucous membranes. Since all the 
above-described pathological processes cease spontane- 
ously a short time after the discontinuance of the remedy, 
it can hardly become necessary to attempt antidotical 
treatment with hydrated magnesia, or the hydrated ses- 
quioxide of iron. From a prophylactic stand-point, how- 
ever, care must be taken that the arsenic is not adminis- 
tered upon an empty stomach, that the usual doses are not 
too rapidly increased, and that its use is not too long kept 
up. 

Auri Chloridum. Auri et Sodii Chloridum. 

The chloride of gold, which, like the officinal chloride of 
gold and sodium, has been highly praised and much em- 
ployed as a specific for syphilis, 3 causes very frequently, 
according to the observations of Chrestien, 4 even in doses 
of 0.006 to 0.003 gram (gr. -^ to -j^), a feeling of burning 
and heat in the skin, gastric disturbances, colic and diar- 
rhoea. The chloride of gold and sodium, according to 
Wibmer, causes, even in doses below the established maxi- 
mal limit, headache, sleeplessness, dryness in the mouth, 
oppression in the region of the stomach, and diarrhoea. 

Others have noticed, after the use of this drug, salivation, 
increased secretion of urine, and exaggerated sexual 
activity. 

1 Charcot, Bullet, de Therapeut., lxvi., p. 529. 

2 Devergie, Eod. loc, lxvii., p. 175. 

3 Legrand, Bulletin de Therapeutique, Decembre, 1846. 

4 Chrestien: De la methode iatraleptique, Ilieme edit. Paris, 1803. 



ALTERATIVES. 99 

The gastric disturbances are explained by the fact that 
albumen is precipitated by the salts of gold, and that the 
double compounds of the chloride of gold with the chlo- 
rine alkalies are readily soluble. They present a close 
resemblance to the disturbances produced by other metals, 
and are due to the action of the drug upon the tissues, 
particularly the mucous membranes of the primse viae. 

Phosphorus. 

Even one small dose, 0.002 gram (gr. -j^), of phosphorus 
may produce in certain cases nausea or vomiting^ 
a sense of weight or pain over the stomach, and in rare in- 
stances icterus, which may persist, it is said, for weeks or 
months. This abnormal action of the drug may be due to 
the method of administration, for it is known that phos_ 
phorus, taken in pilular form or in oil, remains longer in 
the stomach than when it is given in a more readily ab- 
sorbed menstruum, such as chloroform, etc , and this long- 
continued absorptive process may readily excite irritation 
of the digestive organs. For this reason Dujardin-Beau- 
metz, 1 who in tabes dorsalis prescribed the remedy dis- 
solved in chloroform, in capsules, witnessed the occurrence 
of digestive disturbances only after the uninterrupted use 
during eight or ten days, of 0.003 to 0.004 gram (gr. ¥ l 
to -^q). The symptoms disappeared after the temporary 
suspension of the drug, or diminution of the dose. 

IODINIUM. 

In consequence of the extraordinary curative powers of 
iodine and its compounds, and its extensive therapeutical 
employment, the attention of physicians was long ago 
(1820) directed to certain bodily changes, which now and 
then showed themselves during its administration. It is 

1 Dujardin-Beaumetz, "Wiener medicinische Wochenschr. , 1868, p. 767. 



IOO INCIDENTAL EFFECTS OF DRUGS. 

true that a long time elapsed before these incidental effects 
of iodine obtained general recognition, and controversies 
over the existence of such a thing as an " iodine-disease," 
or " iodism," or as to whether its symptoms were to be 
referred to other causes, fill many a page of pharmacologi- 
cal literature. Enlargement of the thyroid gland, among 
other affections, was early subjected to treatment by iodine 
internally and externally, and hence abnormal effects of 
the drug were frequently observed in this affection. There 
was, therefore, no lack of authors J who denied the occur- 
rence of such effects when the drug was used in other dis- 
eases, and attributed the symptoms which so frequently 
appear during the treatment of goitre with iodine, to 
" absorption of the organic substances contained in the 
thyroid gland." The occurrence of iodism was also denied 
on more reasonable grounds. Thus Hjaltelin 2 observed 
that the inhabitants of Iceland, especially those living on 
the coasts, made use of a diet composed principally of 
algas belonging to the class of Laminarias, which are very 
rich in iodine, in the manufacture of which they are 
largely employed. Some persons consume 200 to 250 kilos 
(437 to 547 pounds) of these dried plants yearly. There- 
fore, since 50 kilos (1 10 pounds) of these algas contain at 
least 250 grams ( § viij.) of iodine, these people consume 
annually 1 to 1 J kilo (aj- to 2\ pounds) of iodine, or about 
\\ kilo (3J pounds) of iodide of potassium. In spite of the 
consumption of these large quantities of iodine, Hjaltelin 
noticed in such cases no phenomena which could be attri- 
buted to iodism. However plausible these deductions 
may seem, but little weight should be attached to them; 
for aside from the fact that the quantity of iodine in sea- 

1 Roser, Ueber die sogen. Jodkrankheit, richtiger Krankheit der vertriebenen 
Kropfe. Wurtemb. medic. Correspondenzbl., 18^4, No. 31, and Archiv f. 
physiol. Heilkunde, Bd. vii., 1S48, p. 74. 

2 Hjaltelin, Allgem. medic. Centralzeitung, 1853, p. 745. 



ALTERATIVES. 101 

weed is stated to be five times as great as it really is, the 
circumstance has not been taken into consideration that 
only a relatively small quantity of the plants and their con 
stituents, as is the case with all vegetables, is taken up into 
the fluids of the body, while by far the greater part is not 
utilized, but is discharged with the faeces. For this reason 
these coast-dwellers take into their systems only very small 
quantities of the iodine which is so firmly held in the plants. 
It would lead us too far to consider all the other objections 
which have been raised in this connection. It is now 
positively established that iodine and its salts, after its 
internal or external use, once or repeatedly, in different 
doses, is capable of exciting changes in various organs or 
in the general condition, but only in those who are especially 
predisposed to such occurrences. 

The external application of preparations of iodine causes 
injurious incidental effects only, when they contain free 
iodine, as is the case with ointments of iodide of potassium 
which have turned yellow, Lugol's solution, or the 

Tincture of Iodine. — The local physiological action of 
this preparation upon the healthy skin and mucous and 
serous membranes is well known. It is identical with that 
of the vapor of iodine. The intact skin, under the influ- 
ence of the irritation, is the seat of a feeling of warmth, 
burning and pricking, becoming at first yellow, and, after 
renewed applications, of a dark brownish-red color; then 
dries up and becomes shrivelled, and, after some time, the 
epidermis can be torn off in large flakes. With this nor- 
mal process there are not unfrequently associated inci- 
dental effects, either on the parts treated or on distant 
portions of the skin, in the form of exanthematic affections. 
There appear either rubeola-like, or papular, pustular, or 
even bullous eruptions, which soon heal, with desquama- 
tion, when the use of the agent is discontinued. Thus, 
A. Simon and Regnard, 1 among others, observed, after the 

1 Simon and Regnard, Gaz. medic, de. Paris, 1874, p. 262. 



102 



INCIDENTAL EFFECTS OF DRUGS. 



application of tincture of iodine with glycerin to the 
eczematous scalps of children, an extensive papular erup- 
tion on the face and other parts of the body. This obser- 
vation is confirmed by Badin. 1 This author never suc- 
ceeded in producing albuminuria in adults by painting the 
skin with tincture of iodine ; while the application of the 
agent to portions of the healthy skin not larger than the 
palm of the hand excited this condition in children eight 
or nine years of age. He believes that this difference is 
due to the greater absorptive power of the infantile skin, 
which permits the iodine to enter the circulation as such ; 
while in adults, in whom absorption by the skin takes place 
more slowly, it is taken up in the form of the iodide of sodi- 
um or potassium. This explanation cannot, however, be 
accepted, in view of the disturbances of the urinary appara- 
tus still to be described, which occur after the use of 
iodide of potassium also. 

It will be readily understood that in the local action of 
this agent upon portions of skin deprived of epidermis, as 
well as upon the surfaces of wounds and mucous mem- 
branes, the subjective sensations, as well as the local 
changes, are much intensified. The pains resulting from 
the irritation, which almost equals a cauterization, are 
very severe, although of a transitory nature. The iodine 
coagulates the secretions upon the wound-surfaces or 
in serous cavities, because it enters directly into combina- 
tion with albumen or albuminoid substances, and may, 
therefore, excite violent inflammation, with subsequent ex- 
udation or suppuration. In this case, also, eruptions may 
appear on distant parts of the body — a circumstance which 
proves that iodine may be absorbed from all the parts 
mentioned, and afterwards act upon the skin. 

But the absorption also manifests itself in another unde- 



1 Badin : De l'a'buminur'e consecutive aux applications de teinture d'iode chez 
T enfant. Pa is, 1876. 



ALTERATIVES. IO3 

sirable manner after its external application, viz., by the 
appearance of more remote effects upon certain organs 
and their functions, as well as by a number of symptoms 
affecting- the body at large. These are, therefore, in part, 
identical with those phenomena which often appear after 
the internal administration of iodine-compounds. Simon 
and Regnard (I. a), in addition to the papular eruptions 
already mentioned, noticed coryza and epistaxis after the 
application of iodine. In fourteen cases, they also ob- 
served albuminuria four times, and found iodine in the urine. 
The albuminuria appeared and disappeared with the use 
or discontinuance of the drug. Buckell 1 reports that in 
the case of a lady, who had the tincture of iodine very 
lightly painted upon a tumor between the scapulae, there 
appeared pain and a sense of oppression in the epigastric 
region, and also trembling, weakness, profuse sweating, 
dribbling of urine, and inability to stand erect. The use 
of stimulants and the application of warmth over the sto- 
mach caused these symptoms to disappear in a few days. 
Nelaton, 2 after opening a cold abscess upon a man, injected 
two syringefuls of a dilute solution of iodide of potas- 
sium. Two hours later, there appeared vesical disturb- 
ances, vomiting, thready pulse, swelling of the upper eye- 
lids, pain in the larynx, and on the next day, aphonia, 
croupy cough, and prostration. The administration of ice 
and cathartic pills, and the application of mustard-plasters 
to the extremities and blisters on both sides of the neck, 
caused these symptoms to disappear in three days. 
Fonssagrives 3 has reported a similar case. Two hours 
after the injection of a small quantity of the officinal tinc- 
ture of iodine, diluted one-half, into a traumatically- 
inflamed tunica vaginalis (the fluid which it contained 

1 Buckell, The Lancet, 1st Feb., 1843. 

2 Nelaton, L'abeille medicale, 15 Novembre, 1853. 

3 Fonssagrives, L'union medical, i860, No. 71. 



104 INCIDENTAL EFFECTS OF DRUGS. 

having been previously withdrawn), he witnessed the 
occurrence of a swelling of the scrotum, attended with 
high fever. During the remainder of the day there also 
appeared irritation of the bronchial tubes, discharge from 
the nose, redness of the eyes, oedema of the epiglottis, and 
increased flow of saliva. The fever lasted five days. 

More varied than these more acute symptoms appearing 
after the external application of iodine, are the incidental 
effects which follow the shorter or longer internal admin- 
istration of the drug in medicinal doses. The iodide of 
potassium being generally resorted to for the internal ad- 
ministration of iodine, we shall in this connection consider 
this agent as a representative of all the other compounds 
of iodine. 

POTASSII IODIDUM. 

The first comprehensive data concerning " iodism " 
were published by Rilliet, 1 who distinguishes three forms 
of the affection. According to him, the first occurs acutely 
in all persons of all ages, after large doses, and is due to 
the irritation produced by the agent in the gastro-intestinal 
canal. The second requires a certain predisposition of 
certain organs, and develops gradually in the form of 
slight nervous disturbances, anomalies of secretion of 
different mucous membranes, and affections of the skin. 
The third appears as an iodine-cachexia or constitutional 
iodism, comprises a number of disturbances of the general 
condition and nutrition, and occurs after the prolonged 
use of even minimal doses. Practical observation has,, 
however, shown that such a sharp distinction between 
the different varieties of the affection is not possible, 
because first one and then another group of symptoms 
appears in combination, and also because, in a given case> 
small doses may produce incidental effects, which are usu- 

1 Rilliet, Bullet, de l'Academie de Medec, i860, p. 382. 



ALTERATIVES. 



105 



ally seen only after large doses, and vice versa. It is, 
therefore, evident that, for unknown reasons, sometimes 
one organ and sometimes another is affected in its func- 
tions, or experiences material changes through the action 
of iodine. We are not, however, in a position to construct 
laws from this circumstance, because we are ignorant of 
the conditions necessary for the production of these affec- 
tions. We must, therefore, content ourselves with study- 
ing in detail the various effects produced by iodine upon 
individual organs. 

After taking iodide of potassium, man)' persons experi- 
ence, particularly after waking in the morning, an astrin- 
gent metallic and bitter taste on the tongue. This quickly 
disappears, as Laroche 1 states, after washing the mouth 
with cold water, to which a dessert-spoonful of spirits of 
horse-radish has been added. In very sensitive persons, 
there is also occasionally observed, after small doses, 
tickling and burning, and a sensation of dryness and con- 
striction of the pharynx. In rare cases, disturbances of 
the power of swallowing are observed.- The sensation of 
burning may extend from the throat down the sternum to 
the region of the stomach. With this there is frequently 
associated increased flow of saliva, in consequence of the 
peculiar power of iodide of potassium to excite the secre- 
tion of nearly all the glands. 

Although the function of the stomach is not affected by 
one or more small or medium doses of iodide of potassium, 
even an increase of the appetite to intense hunger being 
sometimes noticed, there is occasionally observed, in the 
case of persons who have a pronounced antipathy to this 
drug, nausea and vomiting, and in others, as Ricord 2 
states, a pain seated at the fundus of the stomach, not 
increased by pressure, and without influence upon diges- 



1 Laroche, Canstatt's Jahresbeiicht f. d. ges. Medicin, 1844, IV., p. 195 

2 Riccrd, Bulletin generale de Therapeut., 1842, p; 161. 



106 INCIDENTAL EFFECTS OF DRUGS. 

tion. Rabuteau attributes these phenomena to adultera- 
tion of the iodide of potassium (IK) with the iodate of 
potassium (KI() 3 ). He claims that, in this case, in conse- 
quence of the influence of the gastric acid, free iodine is 
formed in the stomach, and attacks the mucous mem- 
branes. Although the hypothesis is not altogether satis- 
factory, in view of the fact that these symptoms occasion- 
ally show themselves after taking the pure iodide of 
potassium, it is nevertheless possible that in some cases 
the freshly-liberated iodine may favor their occurrence. 
Therefore, in case doubts arise as to its purity, the iodide 
of potassium should be tested for the presence of the 
iodate, in the manner to be described later. 

Digestive disturbances occur only after the long-con- 
tinued use of large doses of the iodide of potassium. The 
irritative effects of the drug upon the mucous membranes 
of the air-passages, on the other hand, take place so readily, 
that perhaps a majority of those who take it suffer from 
them in a greater or lesser degree. This action is prima- 
rily exerted upon the mucous membrane of the nose, but 
it often occurs simultaneously upon that of the larynx, and 
the bronchial tubes and their ramifications. 

Since the affection first became known, the changes in 
the nose have been called " iodine-cold." It manifests it- 
self in the form of a catarrhal inflammation of the mucous 
membrane of varying intensity, and may spread over its 
whole surface, invading the choanse, the frontal sinuses, 
and the antra of Highmore. The membrane in such cases 
is softened and swollen, secretes freely, and the subjective 
symptoms, which often begin with a burning sensation in 
the nose, take the form, later on, of a feeling of oppression 
and occlusion, sneezing, etc. If the olfactory region is 
particularly affected, loss of smell also occurs. The whole 
affection ends soon after the discontinuance of the drug. 

In the description of the acute pathological symptoms 
produced by the external application of iodine, the occur- 



ALTERATIVES. \oy 

rence of oedema of the glottis has already been mentioned. 
The tendency of the preparations of iodine to excite catar- 
rhal conditions of mucous membranes makes it probable 
that this oedema is due to a sudden swelling of the mem- 
brane of the affected parts, with a subsequent infiltration of 
the submucous connective tissue. The irritation of mucous 
membranes of parts more deeply situated which occurs in 
many persons after the use of small doses of iodide of po- 
tassium renders this view more probable. Thus Ricord 
(1. c.) often observed in such cases a bronchitis which could 
be physically demonstrated, attended with labored respira- 
tion, cough with oppressed breathing, pains in the breast 
and tolerably free expectoration, which, however, never 
became putrid. These respiratory disturbances have 
been by some authors 1 needlessly designated as " iodine 
asthma," in analogy to those previously described as asth- 
matic, occurring after the use of lead, mercury, and other 
metals. But even true oedema of the glottis, as has been 
proven by the observations of Petitjean,' 2 may be pro- 
duced by medicinal doses of iodide of potassium, but 
only in persons already suffering with laryngeal affections 
before taking the drug. In the case of an individual 
who died from such an oedema of the glottis, there 
were found smail ulcers in the larynx, as well as oedema 
of the epiglottis. That pre-existing organic changes 
may be made worse in this manner is proved by a case 
reported by Rodet, 3 of a man suspected to have tuberculo- 
sis, who every time he took iodide of potassium had a more 
or less profuse haemoptysis. 

From an extension of the catarrhal irritation to the vocal 
cords there occurs in very exceptional cases difficulty in 
phonation, without deeper lesions. 

1 Sant'us, Deutsche Klinik, 1856, p. 18. 

2 Pet tjean: Accidents du cote de la peau et des muqueuses determines par 
l'administration de l'jodure de potassium. Paris, 1879, p. 29. 

3 Rodet, Gazette medicale de Paris, 1849, p. 946 



IG 8 INCIDENTAL EFFECTS OF DRUGS. 

Analogous to the pathological changes on the mucous 
membrane previously named, are those which appear with 
tolerable frequency on the eyes and their appendages after 
the use of iodide of potassium. These rarely appear en- 
tirely alone, but are usually attended with nasal or bron- 
chial catarrh, and occur suddenly in one or both eyes, and 
manifest themselves immediately, in part as a catarrhal 
irritation of the conjunctiva and the lining membrane of 
the lachrymal gland and duct. The vessels of the palpe- 
bral and bulbar conjunctiva are greatly injected, the 
mucous membrane itself is swollen and softened, the flow 
of tears is increased, but photophobia occurs but rarely ; on 
the other hand chemosis and oedema of the eyelids some- 
times take place. The subjective symptoms vary with the 
degree of the affection. The patients usually complain of 
burning and itching, and have a feeling as if a foreign body 
were in the eye. In some cases, a painful sensation of 
weight is experienced in the supra-orbital region, at the 
point of exit of the supra-orbital nerve. 

These incidental effects of iodide of potassium may, ac- 
cording to the specific disposition of the individual, appear 
after either one or repeated doses. They usually show 
themselves after the frequent use of small doses, and dis- 
appear spontaneously a few days after stopping the drug, 
without leaving after-effects, and still more quickly if 
mildly astringent lotions are used. Many cases have been 
described in which the above-mentioned symptoms ap- 
peared after 0.5 gram (gr. viiss.) and even less, of iodide of 
potassium. Thus Mecklenburg, 1 among others, witnessed 
after 0.5 gram (gr. viiss.) of this drug, in the course of a 
few hours, intense pains in the eyes, abundant flow of 
tears, burning in the nose and throat, as well as swelling 
and livid discoloration of the upper eyelids, particularly 
in the tarsal region. Twenty-four hours later, all these 

1 Mecklenburg, Berl. klin. Wochenschr., 1866, p. 262. 



ALTERATIVES. 109 

phenomena had disappeared. When only 0.25 gram 
(gr. iv.) of iodide of potassium was again taken, the same 
symptoms, with the exception of the swelling of the eye- 
lids, reappeared in four hours. 

In addition to the purely external phenomena already 
described, it is said that there sometimes appears, although 
very rarely, a limitation of the power of accommodation, 
as well as diminution of the sharpness of sight, symptoms 
of presbyopia. Corlieu 1 reports such a case. He observed, 
in addition to other abnormal effects of iodine, presbyopia 
with dilatation of the pupils and a suddenly-occurring hy- 
permetropia, symptoms which passed away a few days 
after stopping the iodine. Dorval 2 also observed diplopia 
with dimness of sight, and Brera 3 the latter symptom as- 
sociated with orbital pain. Which of the possible factors 
Avas instrumental in causing these disturbances of function 
has not yet been positively determined. 

The already-described irritative effects upon the skin, 
occurring upon distant parts of the body after the external 
application of iodine, also show themselves in many cases 
after the internal administration of the iodide of potassium, 
under widely-varying conditions as regards the dose and 
length of time during which the drug was used. In the 
latter case, however, the multiformity of the eruptions is 
much more marked than in the former. This particular 
incidental effect of the iodide of potassium has been well 
known ever since its introduction into the materia medica, 
and one therefore finds almost innumerable observations 
on this subject in literature. They all go to establish as a 
fact that the iodide of potassium often produces eruptions, 
from simple erythema to petechias, with or without fever, 
occurring either alone or in combination with other ab- 

1 Corlieu, Gazette des hopitaux, Juin, 1856. 

2 Dorval, eod. loco. 

3 Brera, eod loco. 



II0 INCIDENTAL EFFECTS OF DRUGS. 

normal effects of iodine, and disappearing, as a rule, very 
soon after the use of the remedy is suspended. 

These eruptions, according to Fischer, 1 are divisible 
into four principal forms. 

I. The erythematous form. — The skin, particularly on the 
forearms, and also on the face, is reddened, either dif- 
fusely or on circumscribed spots, and its temperature 
elevated. After discontinuing the drug, this symptom 
disappears in a few hours, but if its use be persisted in, 
the eruption may pass into that which is most common, 

II. The urticaria-like form. — Usually on the abdomen and 
extremities, but also on other parts of the body, there ap- 
pear, without fever, intensely red wheals, but slightly 
raised, surrounded by an areola, generally collected into 
groups, only distinguishable from a genuine urticaria by 
their more intense color, which is usually described as 
rose-red, and which become pale on pressure. They dis- 
appear after the use of iodine is stopped, without desqua- 
mation. 

III. The no dulo -pustular form. — This is more rarely ob- 
served, and occurs most frequently in scrofulous individu- 
als, usually upon the upper half of the body. An itching 
spot forms, of a deep-red color, which is soon transformed 
by exudation into a papule, or a bluish-red nodule, with or 
without an areola. This may persist, but as a rule there 
is developed upon it a colored vesicle filled with clear 
fluid, or a pustule, which may burst or dry up, while the 
papule, after the cessation of the use of the iodide of po- 
tassium, slowly disappears with desquamation, often leav- 
ing behind a bluish-red or marbled pigmentation of the skin. 

As intermediate forms pure vesicles, acne-like pustules 
(iodine-acne), and even furuncles are observed. Thus 
Brshesinsky 2 witnessed, in the case of a woman who took 

1 Fischer, Wiener medic. Wochenschr., 1859, No. 29, p. 470'. 

2 Brshesinsky, Canstatt's Jahresber. f. d. ges. Medicin, 1843, iv. , p. 32. 



ALTERATIVES. IIT 

three times daily thirty drops of the tincture of iodine, the 
development of large furuncles with intense surrounding 
inflammation, on the breast and between the shoulder- 
blades. After warm applications they fell off in the form 
of lumps, leaving large ulcers behind. 

IV. The eczematous form. — This is very rare, and appears 
especially on the hairy scalp and in the neighborhood of 
the scrotum. The differential diagnosis between syphilis 
of the skin and this affection is easily made, especially in 
view of the fact that the latter disappears soon after the 
discontinuance of the drug. 

In this connection, for the sake of completeness, mention 
should be made of a form recently described, viz.: 

V. The petechial form. — Fournier 1 describes this eruption, 
which he calls iodine purpura (jodisme petechiale) as very 
rare. He saw the eruption, which has also been mentioned 
by Ricord, in the majority of the cases during the first 
three days after the use of iodide of potassium, more rarely 
from the third to the sixth day. In some individuals it 
always appeared as soon as iodine was administered, and 
in the case of one patient a new eruption occurred every 
time the dose was increased. It appeared in every case 
exclusively on the legs (once only on the trunk) more pro- 
fusely on the extensor than on the flexor surfaces. It never 
attacked the knees or the feet. There are usually as 
many as one hundred discrete patches on each leg. They 
are miliary, usually of pin-head size, rarely as large as a 
bean, and cause no general disturbances of any kind. The 
eruption usually reaches its height in two to three days, 
and lasts at most two to three weeks, and then disappears. 
Petitjean 2 confirms these details in the main, but describes 
a case in which the eruption also occupied the dorsal 
surface of the foot. 

1 Fournier, Revue mens, de Medecine, 1877, p. 653. Vierteljahrsch. f. Der. 
u. Syph., 1878, p. 294. 2 Petitjean, 1. c., p. 35. 



112 INCIDENTAL EFFECTS OF DRUGS. 

Ausspitz 1 saw a similar eruption in a patient who had 
taken twenty -five iodide of potassium pills, each containing 
0.2 gram (gr. iiss.) or in all five grams (gr. lxxv.) 

The best explanation of the occurrence of the above de- 
scribed incidental effects of iodide of potassium is found in 
the view that they are all due to a direct influence of the 
drug (or its products of decomposition) upon the affected 
parts, which it reaches through the blood. The hypothesis 
of " a saturation of the body with iodide of potassium," for- 
merly held by the majority of authors, of which these 
symptoms were considered as the expression, is both so 
obscure and inexact, and so easily refuted by the fact that 
these affections may occur after quite insignificant doses, 
that it is unworthy of further discussion. The results of 
chemical analysis also speak in favor of the local origin of 
these phenomena. 

It has long been known that iodine can be found in 
various secretions, e. g., the urine, saliva, sweat, milk, and 
tears, a short time after taking iodide of potassium. 
Adamkiewicz 2 also succeeded in demonstrating its presence 
in the nasal mucus and in the contents of the sebaceous 
glands in cases of iodine acne, thus showing that the dif- 
ferential diagnosis between this affection and ordinary 
acne may be made by chemical means. In view of this 
discovery, Adamkiewicz attributes iodine acne to the 
action of iodine upon the sebaceous glands. He believes 
that the disease is due to the fact that the salt of iodine 
which is taken into the body forms free iodine in combina- 
tion with the nitrate of ammonium present in the stagnant 
secretions of the skin, and this may irritate the glands and 
the surrounding tissues. The iodine which is discharged 
with the sweat does not produce this affection, as is 
shown by the well-known fact, that the palms of the hands 

1 Ausspitz, Vierteljahrsch. f. Dermatolog. u. Syphilis, 1878, p. 294. 

2 Adamkiewicz, Charite-Annalen, iii., 1876. 



ALTERATIVES. H3 

and soles of the feet are not affected by iodine acne. That 
iodide of potassium should choose these unusual channels 
of exit from the body, instead of the ordinary ones, may 
be due to individual peculiarities, or to the fact that the 
urinary passages, although in a physiological condition, 
perform less work than usual, as in summer, or that they 
are diseased. 

Thus Johnson 1 saw in many cases of Bright's disease, in 
which small doses of iodide of potassium were given, pus- 
tular iodine eruptions, and Rose, 2 after the injection of 
preparations of iodine into an ovarian cyst, found a large 
quantity of the drug in the fluids which were vomited soon 
afterwards. In the latter case, there probably occurred an 
elimination of the drug into the stomach, in consequence 
of a diminished secretion of urine. 

The fact observed by Simon and Regnard (1. c.) that al- 
buminuria sometimes results from the external use of 
iodine, goes to prove that this substance may exert a direct 
action upon the urinary passages. Iodide of potassium is 
said to produce a similar effect in some persons. Rodet 
(1. c.) and Petitjean (1. c.) have reported cases in which 
vesical tenesmus, dysuria, retention of urine, and evert 
hsematuria, followed the use of this salt. 

The old and familiar experience that iodine possesses 
the power of reducing hyperplasia of glandular tissue,, 
finds a physiological analogy in the effect of long-continued 
medicinal doses of iodide of potassium upon the testicles, 
ovaries, and mammae. Many authors claim to have wit- 
nessed under its use the occurrence of varying degrees of 
atrophy in these organs, although they were previously in 
a normal condition. It is probable that a direct localized 
action of the iodine salt or iodine upon the cellular ele- 
ments of the gland is largely instrumental in producing 
such results. 

1 Johnson, British Medical Journal, Jan., 1859. 

2 Rose, Virchow's Archiv, Bd. 35, 1864, p. 32. 



H4 INCIDENTAL EFFECTS OF DRUGS. 

As regards the genital system, it is said that increase of 
the sexual appetite, a discharge of semen, and in women 
more abundant menstruation, may result from the pro- 
tracted use of the iodide of potassium. 

Mention must finally be made of the disturbances of the 
general nervous system and of nutrition which occur in 
some persons after the use of iodine — that group of symp- 
toms which Rilliet has designated constitutional iodism. 
This condition, according to him, may follow the pro- 
tracted use of even minimal doses of the iodide of potas- 
sium. The patients present a peculiar cachectic color of 
the skin, and become much emaciated, although their ap- 
petite is usually good. This condition shows itself in the 
face and about the hips, breast and scrotum, and is asso- 
ciated with a feeling of lassitude and physical weakness, 
and a kind of cerebral confusion which has been called 
" ivresse iodique " by French authors. The patients also 
suffer from derangements of hearing, lancinating pains in 
the extremities, slight spasms of the tendons, and nervous 
palpitation of the heart. 

Although the facts detailed prove that iodide of potas- 
sium often fails to act in a normal manner, causing instead 
undesired incidental effects in the most different organs, 
this circumstance would not justify us in limiting the use 
of this drug, as Rodet proposed, to a small number of dis- 
eases. For these phenomena are observed in only an in- 
significant number of persons, and in the large majority of 
instances they are of merely temporary duration. 

This fact does not exclude the necessity of observing a 
certain amount of caution in administering this remedy, 
especially in cases which already suffer from diseases of 
the larynx or kidneys, and the discontinuance of its use 
on the first appearance of undesirable incidental effects. 

If disorders of the intestinal tract, such as vomiting, 
diarrhoea, etc., appear immediately or a short time after 
taking the drug, it would be advisable to test the purity 



ALTERATIVES. U5 

of the solution used, for which purpose it should be de- 
composed with hydrochloric or sulphuric acid. If the 
iodate of potassium be present, a precipitate is thrown 
down, and free iodine is formed. 

Brominum. 

On account of its disagreeable physical qualities, bro- 
mine is but seldom employed therapeutically. It is, how- 
ever, occasionally used by inhalation, and in watery solu- 
tion as a gargle in infectious diseases, such as diphtheria, 
etc. Besides, on the recommendation of Liebreich, living- 
rooms, which are suspected of being infected, are some- 
times purified by spontaneously volatilizing bromine — a 
method which is certainly preferable to all others, when 
the apartments can be closed and allowed to remain unoc- 
cupied for a long time. For bromine, which, in solution, 
acts as a caustic upon the skin and mucous membranes, in 
the form of a gas irritates the mucous membranes with 
which it comes in contact, exciting changes varying from 
slight redness to violent inflammation. On this account, 
one not unfrequently observes conjunctivitis, coryza, sali- 
vation, a feeling of suffocation, and slight bronchitis with 
cough in those who have inhaled bromine for therapeutic 
purposes, or accidentally, in rooms filled with the vapor. 

The internal use of bromine-water also frequently causes 
coryza, lachrymation, bronchial catarrh, salivation, and 
diarrhoea. In the experiments of Glover 1 upon himself 
with this agent, there appeared only occasionally pains in 
the stomach, and, after larger doses, nausea, hiccough, 
burning in the mouth, oppression over the stomach, etc. 
Experiments of other authors showed that bromine-water 
used in small quantities for a short time, exerts a depress- 
ing influence upon the central nervous system. Those 
who took it experienced a feeling as if ants were crawling 

1 Glover, Edinb. Med. and Surg. Journ., 1842, p. 120. 



Il6 INCIDENTAL EFFECTS OF DRUGS. 

over the skin, drowsiness, apathy, confusion of ideas, and 
weakness of the power of thought and memory. These 
symptoms disappeared immediately after stopping the 
drug. 

POTASSII BROMIDUM. 

In strong contrast with those affections, insignificant in 
number and intensity, which may develop after the use 
of bromine, are a number of incidental effects, produced 
by the internal administration of bromine salts, particu- 
larly the bromide of potassium (and what is true of this, 
applies also to the bromides of sodium and ammonium). 
They present, on the whole, a certain resemblance to the 
symptoms produced by the use of the iodide of potassium, 
but are not of so manifold a nature, and persist, as a rule, 
for a longer time. The mucous membranes are very 
frequently affected, but in a lesser degree than by iodide 
of potassium, while, on the other hand, in many cases, the 
influence upon the skin, and to a still greater extent upon 
the central nervous system, far exceeds in intensity and 
duration that of iodine. 

The fact mentioned in discussing iodide of potassium, that 
the individuality of the affected person is of vital importance 
in determining the occurrence of incidental effects, applies 
also to bromide of potassium. For, while they show 
themselves in some persons after one or more small doses, 
others manifest a certain tolerance for even toxic quanti- 
ties of the agent. In favor of the existence of this want 
of susceptibility, speaks, among others, in a characteristic 
manner, a case reported by Schweig l of a patient who 
manifested no reaction after taking thirty-one grams ( 3 i.) 
of bromide of potassium in seven hours, and after ninety- 
three grams ( 3 iij.) in forty-eight hours, experienced only 
a diminution in the amount of urine excreted, with saliva- 

1 Schweig, Virchow-Hirsch's Jahresber , 1S76, p. 401. 



ALTERATIVES. 117 

tion and somnolence. Arthaud also states that, in fourteen 
cases in which he prescribed doses of from ten to twelve 
grams ( 3 iiss. to 3 iij.) daily, he never saw any affection of 
the skin. 

Bromide of potassium produces, a short time after it is 
taken, a salty, according to others, a bitter after-taste in 
the mouth, and sometimes an increased flow of saliva, due 
to irritation of the buccal mucous membrane and a reflex 
hypersecretion from the salivary glands. In sensitive per- 
sons, there also occur burning in the throat, sometimes 
slight nausea, eructation, and, when it is taken upon an 
empty stomach, pains in the epigastric region, or a sensation 
of oppression, or warmth and fulness. A genuine catarrh 
of the stomach is a rarity, if the drug is not habitually taken 
in an improper manner, upon an empty stomach. One 
now and then observes eructation and vomiting, and more 
rarely diarrhoea, in some patients a short time after tak- 
ing bromide of potassium. On the other hand, as Hutte 1 
first showed, there occur, after long-continued small doses, 
or after larger quantities taken for a short time only, a 
blunting of the sensibility as well as the reflex action of 
the soft palate, the root of the tongue, the uvula, and the 
posterior wall of the pharynx. Gatumeau, 2 after three 
grams (gr. xlv.) of the drug had been taken, observed a 
complete analgesia of the pharynx and epiglottis, so that 
touching the posterior wall of the throat excited no reflex 
movements of swallowing. Krosz 3 also observed in his 
own person, after large doses of the bromide of potassium, 
such a lessening of the reflex excitability of the parts 
mentioned that no reflex nausea could be produced by 
irritating the velum. No less a diminution of sensibility 
is also experienced by the respiratory mucous membrane. 



1 Hutte, Gazette medicare de Paris, 1850, Juin 28. 

2 Gatumeau: These, Montpeilier, 1869. 

3 Krosz, Arch. f. exper. Pathologie u. Pharmakol., Bd. vi., p. 15. 



Il8 INCIDENTAL EFFECTS OF DRUGS. 

This fact, in connection with the not-uncommonly observed 
appearance of bronchial catarrh with copious secretion, 
after the use of bromide of potassium, must not be lost 
sight of during the prolonged treatment of patients with 
this agent, particularly epileptics, maniacs, etc. Stille x 
called attention to the fact that the catarrhs of the air-pas- 
sages, which occur during treatment with bromide of 
potassium, may threaten life, if the use of the agent be 
continued, in consequence of the fact that the diminution 
of the reflex excitability of the respiratory mucous mem- 
brane prevents the occurrence of fits of coughing, which 
might remove the collected mucus. The bronchial catarrh 
is sometimes attended, as Horing 2 found in his own case, 
with pain in the larynx, paroxysms of coughing, and 
hoarseness of voice. According to older authorities, 
haemoptysis also occurs in a large number of patients who 
use this drug, and disappears after its use is abandoned. 
No confirmation of this statement is, however, to be found 
in modern literature. Another accessory symptom of the 
already described effects of bromide of potassium which 
is often noticed, is a foetid odor of the expired air, which 
Veiel 3 has recently called attention to. This cannot be due 
to pathological changes in the mouth, such as occur, for 
instance, after the use of mercury, for bromide of potas- 
sium produces but insignificant alterations in this locality. 
It is probable that the bromine is temporarily separated 
from the potassium in the body, and that the elimination 
of a portion of it by the lungs is the cause of the bad odor 
of the breath. This explanation is not intended to convey 
the idea that the bromine, as such, produces the catarrhal 
changes in the mucous membranes, for even if a small part 

1 Stille, Virchow-Hirsch's Jahresber., 1878, i., p 384. 

3 Horing: Ueber die Wirkung des Broms und seiner Praparate auf den thie- 
rischen Organ'smus. Tubingen, 1838. 

3 Veiel, Vierteljahrsch. f. Dermatol, u. SyphiL, 1875, p 17. 



ALTERATIVES. 



II 9 



of it does leave the body in the form of a vapor, the greater 
part, immediately after its separation from the potassium, 
finds enough of the alkaline metallic salts in the blood to 
be enabled to act upon the different mucous membranes in 
its original character of a bromine salt. 

The mucous membranes of the nose and eyes may also 
be attacked, as is shown by the occasional occurrence of 
coryza, conjunctivitis, lachrymation, etc., after the use of 
bromide of potassium. Dilatation of the pupil is almost 
always noticed after repeated doses. Laborde 1 witnessed 
the occurrence, one or two hours after taking it, of dimness 
of vision and in some cases anaesthesia of the scleral con- 
junctiva. Hiitte (1. c.) stated that myopia, amblyopia and 
diplopia could be produced by bromide of potassium. This 
was also believed by Martin Damourette and Pelvet, 2 while 
Nicol and Mossop claim to have observed dilatation of the 
retinal vessels after its use. These statements are opposed 
to the experiments of Krosz 3 upon himself and others, which 
always gave negative results as regards these pathological 
phenomena. 

It has been demonstrated that the urino-genital appara- 
tus is affected in an extensive degree by this drug. In 
addition to a real increase in the quantity of urine 
excreted, there sometimes occurs, in certain persons, 
strangury , -a constant feeling of fulness of the bladder, 
and also a diminution of the sensibility of the urethral 
and vaginal mucous membranes. The sexual appetite, as 
Rabuteau 4 stated, is diminished by the long-continued use 
of the bromide of potassium. This effect of the drug had 
previously been utilized by Thielmann, 5 who prescribed it 



1 Laborde, Gazette medicale de Paris, 1869. 

2 M. Damourette et Pelvet, Bullet, de Therap., lxxiii., 1867, p. 241. 



3 Krosz, 1 c., p 21. 

4 Rabuteau: Gazette medicale de Paris, 1869, p. 312. 

5 Thielmann, Medic. Zeitung f. Russland, 1854. 



j 20 INCIDENTAL EFFECTS OF DRUGS. 

in doses of 0.18 gram (gr. iij.) as an antaphrodisiac. On 
the other hand, after one large dose, Laborde (1. c.) ob- 
served in himself, sexual excitement, erections and pollu- 
tions. Voisin 1 reports the same^ result as occurring after 
ordinary doses, but very rarely. Sometimes a diminution 
of the catamenial flow occurs in women. 

The irritating effect which bromide of potassium is 
capable of producing upon the skin deprived of epidermis, 
as well as upon mucous membranes, is also manifested in 
a large number of cases after the internal administration 
of the agent, by the production of eruptions of various 
kinds. Their existence has been recognized for a long 
time, and they are usually collectively designated as " bro- 
mine acne," although they occupy a different place in the 
dermatological system. 

Berenguier 2 observed the eruptions in fifty-three per 
cent, Clark and Amory 3 in sixty-six per cent, and Voisin in 
seventy-five per cent of all patients treated with bromide 
of potassium. Some authors, as Bedford Brown, 4 wit- 
nessed their occurrence attended with local or general ele- 
vation of temperature ; while Veiel (1. c.) lays stress upon 
the fact that the acne-like eruption develops very gradu- 
ally, without fever. Voisin found this complication only 
once, in a case of general bromine acne. Falret 5 states 
that he has always found the eruption when four grams 
(3i.) of the salt were taken, but it is certain that it may 
occur after much smaller doses. Children are, as a rule, 
less frequently attacked by it. 

The eruptions produced by this agent are differently 
described by different authors. They are. however, in 

1 Voisin, Bulletin gene'rale de Therapeut , lxxxiii , 1867, p. 241. 

2 Berenguier, Des eruptions provoque'es par l'ingestion des medicaments, 
Paris, 1874, p 14. 

3 Clark and Amory, Virchow-Hirsch's Jahresber., 1872. 

4 Bedford Brown, Virchow-Hirsch's Jahresb., 1873, p. 358. 

5 Falret, Annales Medico-psychologiques, 1871. 



ALTERATIVES. 121 

great part due to affections of the sebaceous glands and 
their consequences, and since the different stages of devel- 
opment are usually represented at the same time in one 
individual, they closely simulate various dermatoses. 
Voisin (1. c.) has given a classification of all the skin-affec- 
tions which occur after the use of bromide of potassium. 
In view of more recent observations by other authors, 
however, his classification may be advantageously in- 
creased by the addition of a few varieties, so that the 
following arrangement may be regarded as comprising all 
the changes of the skin which may be produced by bromide 
of potassium. 

There appear, therefore, in certain individuals, according 
to their specific disposition, independently of sex and 
previous condition of health, at different periods during 
the administration of this drug, and under the widest vari- 
ation as regards dose, various affections of the skin, such 
as: 

i. The erythematous form. — This was observed by Veiel 
(1. c.) as the sole symptom produced by the drug, attended 
with fever, and diffusely spread over the lower extremities. 
The erythema caused the patient great pain. Brown 
(1. c.) also describes this eruption as an effect of bromide of 
potassium. In children he witnessed the occurrence of 
roseola under the same circumstances. 

2. Acne. — This is by far the most frequent form of bro- 
mide of potassium eruption. According to Veiel a thick- 
ened skin, having a greasy look from the free secretion of 
sebaceous matter, as well as the presence of comedones or 
a pre-existing acne, especially predispose to the occurrence 
of this eruption. It appears under different modifications 
which, as regards their seat and their external behavior, 
present a complete analogy to ordinary acne. The first 
step in its formation is usually an erythematous condition 
of the skin of varying extent, attended with pricking and 



122 INCIDENTAL EFFECTS OF DRUGS. 

burning. In this disease also, it is advantageous to distin- 
guish two varieties, acne punctata, and acne pustulosa. 

a. Acne punctata. — This usually precedes the pustular 
form. There appear red elevations, of barley-corn to pea 
size, on a more or less indurated base, surrounded by an 
areola, seated by preference on the face, the eyebrows, 
the hairy scalp, more rarely on the breast and back, and 
almost never on the lower extremities. Veiel found that 
the majority of the nodules were perforated by hairs. 
After a longer or shorter duration, this form may disappear 
with desquamation, or develop into : 

b. Acne pustulosa. — This may be regarded either as the 
result of disintegration of the papules or as an independ- 
ent form of eruption. The pustules are at first of pin-head 
size, of a yellowish-white color, and surrounded by an 
areola. They afterwards increase in size, and in rare cases, 
according to Voisin, may present the aspect of ecthyma- 
pustules. After a few days or weeks, the pustule empties 
out its contents and a firm nodule or a red spot remains 
behind. The number of the pustules varies greatly, the 
whole face being sometimes covered and disfigured by 
them. They may remain for days, or one or more months, 
and if the use of the drug be not stopped, even several 
years ; but they usually disappear in from one to three 
weeks after the discontinuance of the bromide. Voisin 
(1. c.) also noticed that the number of the pustules increased 
or diminished with the increase or diminution of the dose. 
After healing, they often leave depressed, irregularly- 
rounded scars or spots behind. They form on the same 
locations as the nodules previously described, and become 
confluent in some cases, being usually covered with scabs 
on the scalp. Veiel sought in vain for bromine in the 
contents of the acne pustules, but could find it only in the 
urine. Guttmann, 1 in the case of a man who, after using 

1 Guttmann-, Virchow's Archiv, Bd 74, p 540. 



ALTERATIVES. 123 

for one year, at first four grams ( 3 L), later twelve grams 
( 3 iij.) of the bromide of potassium daily, developed a pus- 
tular acne, succeeded in demonstrating the presence of 
bromine in the pustules by the usual method, viz., separat- 
ing the bromine from the potassium by the addition of 
chlorine water to the diluted and filtered pus, and extract- 
ing the bromine by chloroform. 

3. The urticaria-like form was observed a few times by 
Veiel. Wheal-like elevations, varying in size from one- 
quarter to one-half an inch, showed themselves on erythe- 
matous portions of skin. The) 7 were exceedingly sensitive 
to touch, and gradually assumed a wart-like appearance, 
and took on suppurative action. The ulcer thus formed 
became deeper, and had an unhealthy aspect, but disap- 
peared as soon as the bromide was discontinued. This 
form is without doubt identical with the tumor-like 
variety described by Voisin, which consists, according to 
his description, in the appearance of oblong or rounded 
tumors or elevations of the skin, with hard bases, two to 
five centimetres (one and a half to two inches) in diameter, 
and of a rosy-red or cherry color. They show themselves 
only on the legs or calves, and are covered with small yel- 
lowish prominences which, on careful examination, are seen 
to be agminated acne-like pustules, which empty their 
contents in the form of a creamy mass, either spontane- 
ously or when punctured. They are very painful when 
touched, and may be transformed, if the use of the drug is 
continued, into foul atonic ulcers, which last three or four 
months, but if the agent is stopped, disappear in a few 
days. 

Neumann 1 observed the same affection. He proved that 
these tumors are, produced by an inflammation of the 
glands of the skin, attended with an increase of their cellu- 
lar elements and consecutive cell-growth in the cutis, 

1 Neumann, Wiener medic. Wochenschr , 1873, p. 124. 



124 INCIDENTAL EFFECTS OF DRUGS. 

with enlargement of the papillae. During this process the 
hair-follicles are dilated, and appear either as long tubes 
or globular bodies, containing pus, epithelial cells, and 
masses of smegma. 

4. Erythema nodosum. — In two cases out of ninety-six, 
treated for a long time with bromide of potassium, Voisin 
witnessed the appearance on the arms and legs, as well as 
on the body, of patches slightly elevated above the skin, 
of different forms, sometimes having smooth and some- 
times irregular edges. They attained a size of four milli- 
metres to six centimetres (one-fifth to two and a half 
inches), were of a pale-red color in the centre and cherry- 
red in the periphery. They formed and disappeared very 
quickly, and presented the shape, color, and hard base of 
erythema nodosum, but resembled urticaria in reappearing 
when rubbed. 

Veiel states that he has seen such an erythema nodosum 
a few times, but only on the lower extremities. After 
large doses of bromide of potassium, Smith 1 also saw 
patches of the size of a half-dollar, somewhat elevated above 
the surface of the skin, of a bluish-red color, seated upon 
both arms. They bled readily, were indolent, and disap- 
peared soon after the drug was discontinued. 

5. The vesicular form. — Voisin saw in a single case, that 
of a patient who had taken bromide of potassium for more 
than a year, a moist eczema on the thighs. This observa- 
tion stands alone in literature. 

6. TJie fur uncular form. — The coincidence of the use of 
bromide of potassium with the appearance of furuncles 
has been asserted by so many authors that there can be 
no doubt that the two things may stand in the relation of 
cause and effect. Voisin, Smith, and Neumann saw furun- 
cles occur in widely varying numbers, on many different 

1 Smith, Virchow-Hirsch's Jahresbericht, 1879, p. 384. 



ALTERATIVES. 



125 



parts of the body. The latter observed them on the hairy 
portions of the face, and on the forehead and neck. 

It should finally be mentioned that Veiel (1. c.) witnessed 
the appearance of numerous warts on the face and legs of 
a boy, a short time after beginning the use of bromide of 
potassium. 

Various opinions prevail as to the manner in which the 
above-described changes in the skin are produced after the 
internal administration of the bromine salts. Thus Clarke 
and Amory regard bromine-acne as a tropho-neurosis, 
and not as an effect of the eliminated bromide of potas- 
sium, and Veiel, also, does not believe that it is due to an 
irritation of the sebaceous glands produced by the depo- 
sition of bromine in them, having failed to find it there. 
Martin, Damourette, and Pelvet, on the other hand, believe 
the cause of the affection to be the irritation produced 
upon the skin in consequence of the elimination of the 
salt by this channel. The demonstration by Guttmann of 
bromide of potassium in the contents of the pustules, ele- 
vates into a certainty the a priori already probable hypothe- 
sis, that, under certain circumstances, an elimination of 
the salt by the skin may take place. In this way, on the 
one hand, an analogy is established with the similar 
changes in the skin which are excited by the salts of 
iodine, and, on the other, the view is supported that it is 
the bromine in the bromide of potassium which causes the 
affection, and not the potassium, as has been claimed by 
various authors. This is rendered more probable by the 
fact that other bromine combinations exert a similar influ- 
ence. Thus Gowers 1 showed that similar eruptions 
appear after the use of bromide of ammonium, and Stark 2 
saw acne occur in seventy-five per cent of all cases of epi- 
lepsy treated with bromide of sodium, which lasted longer 

1 Gowers, Lancet, 1878, p. 866. 

2 Stark, Zeitschr. f. Psychiatrie, xxxii., p. 148. 



I2 6 INCIDENTAL EFFECTS OF DRUGS. 

than that produced by bromide of potassium, and resulted 
much more frequently in suppuration. He never found 
affections of the skin after a similar administration of 
chlorate of potassium. 

The main treatment of these disorders consists in the 
suspension of the drug. Gowers (1. c.) used Fowler's solu- 
tion in the treatment of bromine-acne, and found that five 
drops daily sufficed to cause the pustules to disappear in 
two weeks. This result was largely imaginary, however, 
since experience teaches that recovery usually occurs in 
this time without treatment. 

Distinct from the previously mentioned transitory inci- 
dental effects of bromide of potassium are a group of 
functional disturbances in the sphere of the central and 
peripheral nervous system, which may be associated with 
one of the affections already described, may persist after 
the use of the drug has been suspended, and may, indeed, 
cause permanent injury to the health of the affected per- 
son. These phenomena constitute the condition known as 
"bromism." 

Voisin distinguishes a chronic and an acute bromism 
and a bromine-cachexia. Intense frontal headache /is usu- 
ally present in all forms of the affection (a symptom 
occasionally observed after the use of bromide of potas- 
sium, without the production of cachectic conditions), and 
bronchial catarrh and cough may also complicate the situ- 
ation. Acute bromism may show itself suddenly, even 
when the drug has been well borne for years, and is 
marked by a staggering gait, mental apathy, a dull expres- 
sion of the eyes, and somnolence, while the chronic form 
is characterized by a sallow color of the face, dryness of 
the mouth, and an unpleasant odor of the breath, emacia- 
tion, diarrhoea, failure to preserve the usual bodily car- 
riage, and trembling of the hands, with weakness of the 
memory and loss of will-power. It may also find expres- 
sion in symptoms affecting the cerebro-spinal system, such 



ALTERATIVES. I2 y 

as delirium, hallucinations, and motor and sensory distur- 
bances. Bromine-cachexia, according to Voisin (1. a), 
begins with loss of appetite, emaciation and somnolence, 
and the condition of weakness associated with it leads, if 
the use of the drug be continued, to the formation of car- 
buncles, or the occurrence of pneumonia, which may prove 
fatal. 

Although this classification is open to the objection of 
being too dogmatic, the fact is nevertheless established 
that all the phenomena which have been described, in their 
most varied modifications, may be produced by the use of 
bromide of potassium. The question as to which of the 
component parts of this preparation is to be regarded as 
the cause 01 these peculiar effects, has, in this case also, 
been differently answered at different times. It may, how- 
ever, be accepted as proven, that they are due to the com- 
bined action of the bromine and the potassium, for Stark 
has shown, by a series of careful observations, that patients 
treated with chlorate of potassium also suffer from certain 
symptoms pertaining to the cerebral sphere, such as con- 
fusion of ideas, diminution of the reflex excitability of the 
throat, uncertainty of motion, etc. Krosz (1. c.) regards 
the bromine as the sole cause of bromism, as far as this 
affects the cerebral and nervous elements, and the potas- 
sium as the cause of the anaemia and the motor distur- 
bances. 

The treatment of bromism should be directed to the dis- 
continuance of the use of the drug, the furthering of its 
speedy elimination from the body, and the ordering of an 
appropriate diet. The physical powers of the patient 
should be strengthened, and change of climate recom- 
mended for the psychical lesions. The rapid elimination 
of the bromide is most readily effected through the kid- 
neys, which are the regular channels for the elimination 
of the halogen salts, and diuretics are, therefore, indicated. 



128 INCIDENTAL EFFECTS OF DRUGS. 

POTASSII CHLORAS. 

Jacobi : has recently called attention to the dangers 
which may attend the use of chlorate of potassium in too 
large doses, and has reported a number of cases in which 
dangerous transitory symptoms occurred, as well as fatal 
results. These observations were confirmed later by 
Marchand, 2 Baginsky, 3 Hofmeier, 4 and Wegscheider. 5 On 
the ground of these facts, Marchand, whose cases, as has 
been shown by Klister, 6 cannot all stand criticism as re- 
gards correctness of diagnosis, demands that chlorate of 
potassium should be entirely abandoned in practice, par- 
ticularly among children. But, if all drugs which pro- 
duce hurtful effects when given in unsuitable quantities, 
or which, when given in ordinary doses, occasionally act 
abnormally, were treated in this manner, the materia med- 
ica would soon be reduced to a minimum. Instead of being 
so ready to dispense entirely with a drug, it would be well 
to exactly determine the doses suitable for different ages, 
and to carefully study the physical conditions which may 
predispose to the occurrence of unpleasant effects. 

Ever since Lacombe ' published a case of the kind, the 
fact has been recognized that chlorate of potassium in too 
large doses may cause fatal poisoning. Isambert, 8 who 
used it for several days in increasing doses of from eight 
to twenty grams ( 3 ij. to 3 v.), afterwards observed a 

1 Jacobi, Gerhardt's Handbuch der Kinderkrankh., ii., p. 764, and the Med. 
Record, 1879, iii., 112. 

2 Marchand, Virchow's Archiv, Bd. 77, p. 456. 

3 Baginsky, Arch. f. Kinderheilkunde, nach einem Vortrage vom 10. Novem- 
ber, 1878. 

4 Hofmeier. Deutsche medicin. Wochensch , 1880, Nos. 38 and 39. 

5 Wegscheider, eod. loco, No. 40. 

6 Kuster Berlin, klin. Wochenschr , 1880, No. 40. 

7 Lacombe, Jour, de Medecine de Bruxelles, 1856. 

8 Isambert: Etudes chimiques, physiol. et cliniques sur l'emploi the'rap. de 
Clor. de Potasse. Paris, 1856. 



ALTERATIVES. i2 q 

greenish color of the stools and an increased flow of urine, 
with a feeling of oppression and pain over the kidneys. 
Ten minutes after it was taken, he could find it in the 
urine, the elimination lasting one or two days. 

The cases of poisoning reported by these authors pre- 
sent a number of analogous symptoms, equalling in dan- 
ger those caused by the most active poisons. These are : 
obstinate choking and vomiting, icteric discoloration of 
the skin, pains in the stomach and over the kidneys, and 
occasionally epistaxis, and diminution in quantity and 
even suppression of urine, lasting from one day to a day 
and a half, hematuria and albuminuria. With these symp- 
toms may be associated sleeplessness, a feeling of alternate 
cold and heat without demonstrable fever, a small rapid 
pulse, and violent hiccough, and death may occur in a 
comatose condition. In the case reported by Wegschei- 
der, there appeared, on the seventh day after the poison- 
ing, at first only on the arms and forehead, a few red, not 
elevated spots, of the size of a pea, which became momen- 
tarily somewhat paler under pressure, and spread in the 
course of the next three days over the whole body, becom- 
ing larger, and of a copper-red color. 

These observations should be contrasted, however, with 
the fact that hitherto no case has been recorded in litera- 
ture, in which the administration of chlorate of potassium 
in medicinal doses was followed by injurious incidental ef- 
fects similar to those just described, with the exception of 
the digestive disturbances. As medicinal doses we regard 
those proposed by Falck, 1 0.1-0.5 gram (gr. ij.-viij.) at 
once, or five grams (gr. lxxv.) daily, or those of Jacobi (1. a), 
for a child of from one to three years of age, one to two 
grams (gr. xv.-xxx.) daily, and for adults six to eight grams 
(3 iss.-ij.). 

Of course we leave out of consideration, in this connec- 

1 Falck: Uebersicht der Normalgaben der Arzneimittel. Marburg, 1875, p. 10. 
9 



130 INCIDENTAL EFFECTS OF DRUGS. 

tion, those cases in which no positive opinion can be 
formed as to whether a pre-existing dipththeritis or the 
chlorate of potassium prescribed for it has caused the 
threatening symptoms, or the death. Whenever the doses 
exceed the usual limit, a number of incidental effects may 
be produced, such as Marchand describes in his second 
observation. A boy from three to four years of age, suf- 
fering from stomatitis, who took at least ten grams ( 3 iiss.) 
of chlorate of potassium in one day, was attacked by 
drowsiness, vomiting, diarrhoea, and delirium. He also suf- 
fered from epistaxis, and passed bloody albuminous urine, 
containing a granular brownish sediment. Recovery took 
place in fourteen days. 

The treatment of such cases can be only symptomatic. 
Emptying the stomach of any of the poison which it may 
contain, quieting the vomiting by ice-pills, champagne, 
etc., the administration of demulcent drinks, in order to 
act upon the affected kidneys, constitute the therapeutic 
measures to be employed. 

Potassit Chloridum. 

The chloride of potassium, which Sander 1 considers of 
equal value with the bromide of potassium, is said by him 
to have the advantage over it of producing no incidental 
effects. Further investigations have not confirmed either 
statement. For Stark 2 found, as has already been stated, 
that chloride of potassium has no effect whatever upon 
epileptic attacks, and that, on the other hand, it may, in 
certain individuals, in medicinal doses, produce a series of 
hurtful incidental effects in the same way as bromide of 
potassium. These consisted of a mild degree of confusion 
of ideas, drowsiness, torpidity, pains in all the limbs, di- 
minished power of motion, difficulty of speech, loss of 

1 Sander, Centralbl. f. d. median. Wissenschaften, 1808, No. 52. 

2 Stark, Zeitschrift f. Psychiatrie, xxxii., p. 159. 



EXCITANTS. 



131 



appetite, and in one case also a complete suspension of the 
reflex excitability of the pharynx. While these symptoms 
lasted, the frequency of the pulse was much diminished. 

Potassii Sulphas. 

The external application of the alkaline sulphates, partic- 
ularly the sulphate of potassium, in the form of ointments, 
lotions and baths, causes not infrequently, in certain per- 
sons especially predisposed thereto, an irritation of the 
skin whose intensity is in proportion to the quantity of the 
salt used. 

According to Bazin 1 small, intensely painful, confluent 
vesicles are formed upon a reddened base, which become 
filled with a serous or purulent fluid, and are surrounded 
with an areola two or three times as large as their diame- 
ter. This affection disappears in a few days. 

More serious symptoms may also be produced by the 
inunction of sulphate of potassium. Thus Bazin, 1 after 
four or five applications to the lumbar region of a solution 
of four grams ( 3 i.) of sulphate of potassium in thirty 
grams (fl. 3 i.) of water, witnessed the occurrence of a vio- 
lent phlegmonous inflammation, with the formation of 
pustules and abscesses. Strange to say, the skin of the 
thighs and buttocks, upon which the remedy was applied 
in the same manner, was affected by the inflammation in 
only a slight degree. 

EXCITANTS. 

Camphora. 

Upon the mucous membrane of the mouth camphor 
produces a biting, later a burning taste, and a subsequent 
feeling of coldness extending down to the stomach. If it 
is held in the mouth for some time, there appear symp- 

1 Bazin, Lecons sur les affections cutane'es artificielles. Paris, 1862, p. no. 



132 



INCIDENTAL EFFECTS OF DRUGS. 



toms of irritation of the mucous membrane, such as pain, 
swelling, etc. The power of the drug to cause pain is also 
exerted when it is applied to the surfaces of wounds. 

The effects produced by the internal administration of 
camphor in medicinal doses, differ, as Jorg 1 discovered, 
according to the individuality of the person. While some 
persons experience no abnormal sensations after 0.3-0.5 
gram (gr. v.-viij.), in others there appear, even after doses 
of 0.03-0.06 gram (gr. j^-i.), headache, dizziness, slight 
confusion of ideas, redness of the face, dryness of the 
mouth, and thirst. 

The alcoholic solution of camphor is said to act more 
powerfully than the drug in substance. Purkinje 2 ob- 
served in himself, after doses of 0.5 gram (gr. viij.) a pleas- 
ant excitement and liveliness, similar to intoxication, a 
desire for active motion, and a slight pricking in the skin. 

While these symptoms rapidly disappear, as a rule, 
without leaving any unpleasant after-effects, the phenom- 
ena which not unfrequently follow the administration of 
camphor per enema are more serious, last longer, and de- 
mand therapeutic interference. There occur vomiting of 
masses smelling of camphor, strangury, heat, clammy 
sweating (the sweat also smelling of the drug), increased 
frequency of the pulse, and a condition of psychical exal- 
tation, which may result in delirium. 

In such cases, enemata of senna and sulphate of sodium, 
sinapisms to the neck and body, cold applications to the 
head and cold douches, are indicated. 

Moschus. 

The statements concerning the incidental effects of 
musk are to a certain extent contradictory. After doses 



1 Jorg: Materiallen zu einer Arzneimittellehre. Jena, 1827, p. 230. 

2 Purkinje, Neue Breslauer Samml., 1829, I., p. 428. 



EXCITANTS. 



133 



of 0.06-0.25 gram (gr. i.-iv.), Jorg 1 observed, in those upon 
whom he experimented, slight headache, particularly in the 
frontal region, confusion of ideas, giddiness, and oppres- 
sion in the orbital fossae. As regards the digestive canal, 
Jorg himself, after 0.18 gram (gr. iij.) experienced oppres- 
sion in the stomach, and eructation with a penetrating 
odor of musk, and other observers noticed burning and 
dryness in the throat. Trousseau and Pidoux, 2 on the 
other hand, after the same dose, felt only a peculiar sensa- 
tion of warmth in the stomach and abdomen, which after- 
wards changed into a decided sensation of hunger. 
Some time later they experienced pains in the temples and 
occipital region, dizziness, and excitement of the sexual 
organs. 

According to the observations of Mitscherlich, 3 vomiting 
without digestive disturbances occasionally occurs after 
small doses of musk. This is probably due to a subjective 
aversion to the drug. Diarrhoea has also been observed 
after its use. 

Radix Valerianae. 

The root of Valeriana officinalis, by many regarded as 
inert, is capable, as shown by the experiments of Jorg (1. c.) 
of producing unpleasant symptoms in some individuals, 
even in small doses. This author sometimes observed the 
following symptoms, either alone or combined, after the 
administration of four to twelve grams (3 i. to 3 iij.) of an 
infusion of valerian root : tickling in the throat, eructation, 
nausea, headache, especially in the frontal and parietal re- 
gions, a feeling of constriction of the pharynx, rumbling in 
the abdomen, diarrhoea, colicky pains, and anorexia. 



1 Jorg, 1. c. p. 285. 

2 Trousseau et Pidoux: Traite de Therap., III. Edit., II., p. 193. 

3 Mitscherlich: Lehrbuch der Arzneimittellehre. Berlin, 1849, Bd. II., p. 369. 



134 INCIDENTAL EFFECTS OF DRUGS. 

Barbier 1 witnessed the occurrence of hallucinations of 
sight in a person treated with this agent. 

Flores Arnice. Tinctura Arnic.e. 

In some persons, irrespective of the mode of employment, 
even small quantities of arnica may cause disagreeable ac- 
cidents. Infusions of 0.3 to 1.0 : 120.0 grams of water 
(gr. iv.-xv.: fl. \ iv.) not infrequently produce burning and 
tickling in the throat and mouth, pains in the stomach and 
abdomen, eructation, and occasionally rectal tenesmus and 
diarrhoea. There also occur oppressive headache, a sen- 
sation of fulness, giddiness, and unquiet sleep. 

Wilkinghoff 2 has recently shown that when arnica is 
kept for some time, its active principle may grow weaker 
and finally become inert. This fact explains the differ- 
ences which have been observed, in the action of the drug. 

It seems that the symptoms detailed, affecting the primse 
viae, are due to a local irritant action of the drug, and that 
the nervous disturbances are of a reflex nature. This 
view is sustained by the fact that if the tincture of arnica 
is applied to the healthy human skin, there may appear, 
in accordance with the strength of the preparation, either 
itching and burning, and later redness of the affected parts, 
or miliary or pea-sized vesicles may develop upon a red- 
dened base, or even well-formed bullae. These changes 
are followed by corresponding general symptoms. 

NARCOTICS. 

Opium. 

In the case of no other medicinal agent are the individ- 
ual relations of the patient so influential in determining 

1 Barbier: Matiere medic, 1824, II., p. 83. 

2 Wilkinghoff: Median. Be ; trage zur Kenntniss der Arnica montana. Jnaug. 
Diss., Bonn, 1880. 



NARCOTICS. I3 5 

the occurrence of an abnormal mode of action as in that of 
opium. Among the more important of these relations are 
the nature of the disease, the age and sex of the patient, 
and, according to Charvet, 1 even the climate in which he 
lives, and the race to which he belongs ; in short, that 
peculiar ready susceptibility to the unusual action of a 
certain drug which is dependent upon definite physical 
-considerations, and which, in a given case, is very difficult 
of detection. 

As regards the age of the patient, it should be stated 
that, in the cases of many children, injurious, and some- 
times even fatal incidental effects may very readily follow 
the administration of opium. A knowledge of this fact 
has, therefore, for a long time caused it to be held as an 
axiom, that opiates should be but sparingly used in the 
treatment of children. In recent times, however, this 
teaching of experience has been frequently ignored, the 
dangers said to result from the use of such agents being 
regarded as exaggerated, even if not absolutely destitute 
of foundation. Nevertheless, that this warning is well 
grounded, and that a cautious use of these agents is indi- 
cated in such cases, is proved by the large number of 
accidents of this nature found in literature, occurring after 
moderate, and even the very smallest doses. Sobotka, 2 
among others, reports several cases in which serious symp- 
toms of poisoning appeared after almost minimal doses of 
opium, and one case of death after the administration of a 
few dessert-spoonfuls of a mixture containing three drops 
of laudanum and fifteen grams (fl. 3 ss.) Syrup. Papaver. 
alb., diluted to one hundred and eighty grams (fl. § vi.). 
After still smaller doses, 0.0006 to 0.0003 gram (gr. yi 
to -j^o), Edwards, 3 and also Smith, 4 saw fatal results occur. 

1 Charvet : Die Wirkung des Opiums auf die thier. Oekonomie. Leipzig, 
1872. 2 Sobotka, Journ. f. Kinderkrankh., Dec., 1845. 

3 Edwards, in Taylor : Die Gifte. 

4 Smith, Medical Times and Gaz., 1854, April 15th, p. 386. 



136 INCIDENTAL EFFECTS OF DRUGS. 

A large number of similar observations has been collected 
by Taylor. 1 

In women also, in consequence of their greater sus- 
ceptibility to irritation, abnormal effects are much more 
easily produced by opium than in men, caeteris paribus. 
Gastric disturbances and cerebral hyperasmia are also fac- 
tors which may exercise a favoring influence upon the 
occurrence of incidental effects. But constitutional bod- 
ily conditions, above all other things, are capable of 
modifying the normal effects of opium, or of producing 
undesirable symptoms. 

The incidental effects hitherto described may show 
themselves after any manner of using opium. They seem 
to occur most readily, however, after its administration 
per enema, for numerous observations have been reported 
of cases in which threatening symptoms, or even death, 
occurred after enemata containing very small quantities 
of opium. Whether, as Dupuytren believed, a more rapid 
and complete absorption of opium takes place in the intes- 
tines than in the stomach, and, therefore, a more intense 
action of the drug occurs, has not yet been experimentally 
determined. 

The central nervous system is first to be considered 
among the points of attack of opium. There not unfre- 
quently occur in some persons, even after doses of 0.015 
to 0.05 gram (gr. ^-f), a feeling of excessive fulness of the 
head, dizziness, and headache, lasting several hours or 
even a number of days, seated sometimes in the frontal 
and sometimes in the occipital region. These symptoms 
were known to physicians of antiquity, such as Scribonius 
Largus and others. Tralles, 2 who reported such an obser- 
vation upon a man, says in not very classical Latin : . . . 
per multos dies ponderosissimum caput circumgestasse." 

1 Taylor: Die Gifte, iibersetzt von Seydeler. Coin, 1863, Bd. iii , p. 31. 

2 Tralles : Usus opii salubris et noxius, Vratislav., 1774. 



NARCOTICS. 137 

Convulsions are also said to have been produced by medi- 
cinal doses of opium. After larger doses, but still less 
than the maximum, there have been noticed buzzing and 
ringing in the ears, confusion of ideas, dimness of vision, 
disturbances of hearing, and partial or complete uncon- 
sciousness. The motor sphere may also be affected, there 
occurring in some cases, as Albers a stated, spasm of ten- 
dons, particularly of the extensor muscles, tremor of the 
hands, jerking, weakness, and even temporary paralysis, of 
the legs. Disturbances in the digestive apparatus may also 
appear, either simultaneously with these symptoms or as 
independent effects of the action of opium. The mouth 
and throat become dry, nausea and vomiting occur, and 
the appetite is lost. The latter, however, occurs in many 
cases only after repeated doses of the drug. 

The changes which sometimes occur in the skin, after 
the use of opium, are especially worthy of study. Aside 
from the sometimes very profuse sweating which takes 
place, the face is congested, intensely reddened, and the 
rest of the skin feels hot to the touch. Annoying itch- 
ing, without eruption, may also be present. This " pruritus 
opii " was mentioned by Dioscorides, 2 Paulus ^Egineta, 3 
and also by authors of the last century, and described as 
a tormenting and unbearable affection. 

In rare cases, an eruption, with or without pruritus, is 
noticed after th'e use of opium. The first recorded obser- 
vations on this subject emanated from Tralles; 4 who 
believed that the eruption bore a certain relation to the 
sweating which appeared simultaneously with it. The 
presence of the latter symptom is, however, not essential 
to the production of the exanthema. Duclos 5 lays spe- 

1 Albers, Virchow's Archiv, Bd. 26, p. 225. 

2 Dioscorides : De noxiis venenis, Cap. xxiii. Venetiis, 1516, p. 124. 

3 Paulus ^Egineta : Opera. Lugduni, 1551, lib. v., cap. xliii., p. 355. 

4 Tralles, 1. c, p. 137 and 138. 

5 Due os, Journ. de Medec, Septem., Novembre, 1846. Ref. in Schmidt's 
Jahrb., Bd. 64, 1849, p. 74. 



138 INCIDENTAL EFFECTS OF DRUGS. 

cial stress upon the fact that this may occur without aug- 
mentation of the secretion of the skin. 

The eruption produced by opium consists usually of 
small, red, isolated spots, resembling in form that of mea- 
sles. According to an observation of Rieken, 1 these spots 
may spread diffusely over the whole body, and thus pre- 
sent the appearance of scarlatina. Even the mucous 
membrane of the mouth and throat, this author states, 
maybe attacked by this ''erythematous inflammation." 
He witnessed the occurrence of such an eruption on a 
man every time he took opium internally, and even after 
the employment of ointments and collyria containing it. 
According to Berenguier, 2 the erythematous spots show 
themselves shortly after taking the drug, on the face, neck, 
arms, and breast, and disappear without leaving traces of 
their presence behind. Behrend 3 has also recently stu- 
died an opium eruption. It appeared after taking a few 
powders containing 0.015 gram (gr. £) of opium with 0.5 
gram (gr. viij.) of sugar, accompanied with violent itching, 
on the chest from the clavicles to the lower end of the 
sternum, on the inner surfaces of both upper arms, the 
flexor surfaces of the forearms, and over the wrist-joints, 
spreading down the thighs, from the neighborhood of the 
adductors to the popliteal spaces, and the posterior and 
inner aspects of the legs, terminating at the ankle in a 
stripe of livid color, about three fingers in width. It ap- 
peared as a pale scarlatina-like redness, which spread dif- 
fusely over the surrounding healthy skin, and, on closer 
examination, was seen to be composed of papules of pin- 
head size, lying close together. Several days after the 
eruption had passed away, there occurred a fine branny 



1 Rieken, Schmidt's Jahrbucher, Bd. cvii., p. 22. 

2 Berenguier : Des eruptions provoquees par l'ingestion des medicaments. 
Paris, 1874. 

3 Behrend, Berl. klin. Wochensch. , 1879, P- 626. 



NARCOTICS. 



139 



desquamation of the epidermis. Brand ' also observed an 
eruption which spread over the trunk and flexor surfaces 
•of the body, was attended with intense itching and high 
fever, and presented the appearance of a diffuse redness* 
made up of innumerable small points. In this and a simi- 
lar case, there appeared, after eight days, a desquamation 
in the form of flakes of various sizes, which lasted nearly 
ten days. 

The mode of occurrence of this exanthema is probably 
the same as that of all other drug eruptions. In the pres- 
ent instance, also, we may regard a direct action of the 
drug upon the affected portions of skin, or upon its tro- 
phic nerves, as the cause of the disease. This view, at 
least, aids us in forming an opinion as to the ultimate 
cause of the affection, although we are still unable to ex- 
plain why only certain persons, and only certain portions 
of the bodies of those persons, are attacked. Although 
Behrend (1. c), in describing the case of disease already 
alluded to, states that the occurrence of the opium erup- 
tion in consequence of a possible elimination of the drug 
by the skin, or even as an effect of its presence in the vessels 
of this organ, is to be excluded " with absolute certainty," 
this assertion must be regarded as absolutely unproved, its 
only force lying in the positiveness with which it was 
made. His supposition, that eruptions from opium and 
other drugs occur in consequence of some mysterious 
change produced in the blood by these agents, leads to 
absolutely untenable hypotheses, and would, even if it were 
correct, be likewise ultimately dependent upon a local 
action of the " dyscrasic blood " upon the skin. 

As regards the therapeutics of the incidental effects of 
opium, recovery occurs spontaneously, as a rule, on the 
stoppage of the drug. If threatening symptoms, such as 
sopor, etc., have occurred, external excitants, stimulants, 

1 Brand. Berl. klin. Wochenschr , 1879, p. 718. 



I40 INCIDENTAL EFFECTS OF DRUGS. 

ice, cold baths, sinapisms, etc., should be employed. Ac- 
cording- to Da Costa, 1 bromide of potassium possesses the 
power of preventing the incidental effects of opium, par- 
ticularly the fainting, headache, dizziness, and nausea, and 
also of lessening the itching of the skin, when taken in 
doses of two to three and a half grams (gr. xxx. to 1.), a few 
hours before the opium. 

Morphia. 

What has been said of opium applies in the main to its 
most active constituent, morphia, and its salts. After its 
use also, headache, stupor, and particularly nausea and 
vomiting are observed. Thus Billroth, 2 in the case of a 
lady who took small doses, 0.007 gram (gr. ■£), and even 
0.003 gram (gr. J^-), saw such anxiety, nausea, and vomit- 
ing, that, although suffering intense pain, she refused to 
take the remedy again. Laborde attributes the vomiting 
to the bad quality of the morphia, which after a time 
becomes partially transformed into apomorphia. How- 
ever, no careful chemical investigation of this subject has 
yet been made. 

Wernick 3 has called attention to the occurrence of a 
parsesthesia of taste after the use of morphia, which,, 
according to his observations, is especially liable to occur 
in patients much reduced in health, and in robust persons 
after prolonged inanition, and is probably due to a centraL 
irritation analogous to that set up by santonin. The 
affected persons, shortly after the injection, complain of an 
intensely bitter or sour taste in the mouth, which usually 
ends simultaneously with the cessation of the morphia 
action. 

The incidental effect which morphia sometimes pro- 

1 Da Costa, Virchow-Hirsch's Jahresb., 1871, i., p. 307. 
' 2 Billroth, Wiener medicin. Wochenschr. , 1868, p. 763. 
3 Wernick, Archiv f. Psychiatrie, Bd. ii., p. 174. 



NARCOTICS. I4I 

duces on the eyes has been carefully described by v. 
Graefe. 1 There occurs, particularly in very irritable per- 
sons, a spasm of the accommodation, the result of the stimu- 
lating influence of the drug upon the ciliary muscle. The 
focal point approaches so near that the range of accommo- 
dation is much limited, and myopia therefore occurs. 
Sommerbrodt also observed spasm of the accommodation 
lasting only thirty seconds, after the injection of o.oi 
gram (gr. -J-) of morphia. The outlines of the faces and 
heads of persons standing around the bed seemed to the 
patient to suddenly run together, so that he was unable to 
recognize any one. Although, according to v. Graefe, 
this condition usually appears thirty to forty-five minutes 
after the injection, in this case it presented itself immedi- 
ately after it. 

The skin may also be affected by morphia, as is shown 
by the occurrence of itching and eruptions after its use. 
Thus Apolant 2 saw in the case of a man who took several 
times twelve to fifteen drops of a solution of Morphias 
mur., 0.08 (gr. ij), in Aquae Amygdalar., 10.0 (fl. 3 iiss.), an 
urticaria-like eruption, which the patient, without know- 
ing what he had taken, at once attributed to morphia, 
having already discovered that he was specially suscepti- 
ble to its incidental effects. The eyelids were swollen, the 
whole face cedematous, and red, wheal-like prominences 
appeared on the hands and other parts of the body. After 
five days, desquamation set in, during which large, coher- 
ent pieces of epidermis could be pulled off. 

A distinction should be made between the true inci- 
dental effects of morphia already mentioned, and the 
symptoms which frequently appear without their cause 
being clear, after the direct intra-venous injection of the 

drug, in consequence of the canula being accidentally 
c ~ f 

1 V. Graefe, Archiv f. Ophthalmologic, Bd. ix., 2, p. 62. 

2 Apolant, Berl. kMn. Wochenschr., 1877, p. 361. 



T 4 2 



INCIDENTAL EFFECTS OF DRUGS. 



thrust into a vein. In such a case, there occur, as 
Chouppe 1 states, redness of the face, heaviness and a feel- 
ing of fulness of the head, increase in frequency of the 
pulse to ioo, great anxiety, and cold sweating. These 
symptoms last but a few minutes, and can be prevented 
by withdrawing the canula a little after introducing it r 
and by making the injection only when no blood flows 
from its opening. 

In this connection we shall consider that pathological 
condition produced by the habitual use of opium or mor- 
phia, which has been made the subject of such thorough 
study, and is so frequently discussed in modern literature. 

Opium Eating and the Morphine Habit. 

The phenomena which manifest themselves after the 
prolonged use of opium in increasing doses, are analogous 
to those produced by the internal or subcutaneous em- 
ployment of morphia. The quantities which can be taken 
for a long time without injury by some persons must be 
regarded as simply enormous, when we consider how 
little of the drug is necessary to produce dangerous or 
even fatal poisoning in a normal system, and the state- 
ments as to their amount would be received with incredu- 
lity, if we were not forced to accept them as absolutely 
proven. The tolerance for such otherwise certainly fatal 
doses is produced by habituation to the action of the 
poison, and can be established only by beginning with 
small doses, and gradually increasing them. The opinion 
is justifiable that, in this manner, those cell-groups, whose 
functions are usually only temporarily affected by opium, 
are deprived of their energy by the chemical or physical 
influence continually brought to bear on them, or, in other 
words, that they constantly require a fresh stimulus of 

1 Chouppe, Gazette hebdomad, de Medecine et de Chirurg., Mars, 1876, p. 
162. 



NARCOTICS. 



143 



increasing strength, in order to manifest the same func- 
tional capacity as formerly, and, at the same time, are pro- 
tected against the danger of a poisonous action of the 
drug causing the irritation. A point must, however, be 
finally reached, at which the quantity administered no 
longer suffices to excite or restrain the functions of certain 
organs, and when a still further increase of the dose causes 
such profound changes in the organ itself, or in others, by 
a reflex or sympathetic action, that the symptoms of poi- 
soning and its consequences appear. 

These affections may be developed by the frequent 
therapeutic employment of opium or morphia. The 
patient, who has learned to appreciate its power of reliev- 
ing pain, has recourse to the drug whenever opportunity 
offers, even in insignificant bodily ailments, in order to 
relieve conditions for which another would hardly seek 
medical aid. Thus the first step is taken upon the road 
which leads unalterably to the vicious use of these nar- 
cotics. For when unpleasant bodily conditions which 
might furnish an occasion for their use are lacking, there 
appear at first psychical emotions, such as sorrow or care, 
and later slight mental disturbances, anger, vexation, etc., 
take their place (for opiates in suitable doses produce 
happy forgetfulness, lasting for hours, or an agreeable 
alienation of consciousness). When even these induce- 
ments are lacking, the constantly diminishing capacity for 
work, the neglect of social and family duties, as well as 
numerous other alterations of the emotional nature and 
the bodily functions, furnish an excuse for still further 
increasing the dose, until bodily and mental marasmus, or 
natural or violent death, puts an end to the wicked prac- 
tice. 

Before the more rapidly and powerfully acting morphia 
came into such extensive employment as at present, the 
above-described phases of the abuse of narcotic drugs 



44 



INCIDENTAL EFFECTS OF DRUGS. 



were observed, either singly or collectively, after the use 
of opium. Flemming 1 furnishes a striking description of 
the moral condition and the physical sufferings of opium 
eaters. He shows how a confession of their vice can be 
drawn from such persons only by strategy, that they are 
lost to every feeling of shame, and how social and family 
ties are loosened by this passion. In advanced degrees of 
this vice, there occur depression or excitement of spirits, 
childish impatience, incapacity for thought or inability to 
fix the attention upon a certain object, a want of sympathy 
for the affairs of daily life, clouding of the memory, and 
Aveakening of the power of judgment. At the same time, 
bodily disturbances appear, among others, inability to 
sleep, gnawing pains in the stomach, loss of appetite, a 
feeling of chilliness with sweating, and not infrequently 
derangements of the sexual activity. 

The same symptoms are produced by morphia taken 
internally. In a case reported by Samter, 3 it was taken 
for three years, and during a period of three hundred and 
twenty days, in which the patient was constantly under 
careful observation, he consumed 79.5 grams ( f iiss.) of the 
agent. Eder 3 saw still larger doses taken. The patient 
observed by him took laudanum for six years, in increas- 
ing doses to thirty grams (fl. 3 viiss.) daily, for eighteen 
months pure opium, at first one gram (gr. xv.), later as 
much as nine grams (3ij. gr. xv.) daily, and for six 
months morphia, beginning with 0.4 gram (gr. vi.) and 
increasing to 2.6 grams (3 ij.) daily. 

The introduction of the practice of injecting morphia 
subcutaneously, and the habit of intrusting the syringe to 
the control of the patient, his friends, or the nurse, has 
undoubtedly largely contributed to the spread of the mor- 

1 Flemming, British Medic. Journal, Feb. 15th, 1868, p. 177. 

2 Samter, Deutsche Klinik, 1864, 16, 17. 

3 Eder, Oesterreichische Zeitschrift f. pr. Heilkunde, 1864, No. 33. 



NARCOTICS. 



145 



phine habit, although we have not yet gone so far as to 
justify us in saying with Bouchardat, 1 "que le morphi- 
nisme fait a Berlin de tels progres qu'il y a des maisons de 
sante speciales pour en recueillir les victimes." 

Observations on this subject have greatly increased in 
number during the past few years. From America, Mat- 
tison 2 has called attention to the abuse of morphia which 
prevails in that country. In Germany, Lahr 3 and Fiedler 4 
were the first to raise their voices against the spread of 
this vice and to attribute the blame for it, in part at least, 
to physicians. At the same time with Fiedler, L. Lewin 6 
described a case of morphinism. More recently Levin- 
stein 6 has treated this condition most exhaustively, basing 
his remarks upon a large number of observations, and 
after him Burkart 7 communicated his views upon the 
subject. 

All cases present in an equal degree a gradual continu- 
ous decline of the psychical life, and also a series of bodily 
disturbances similar to those which we have described in 
connection with opium, and as incidental effects of mor- 
phia. As exceptional symptoms, there appear in some 
cases slight, transitory albuminuria or glycosuria, such as 
occurs in other conditions of chronic intoxication. The 
morphia habit should be regarded as such a condition, and 
we cannot share the opinion of those who are inclined to con- 
sider as diseases sui generis, either single groups of symp- 
toms, or the sum of all the pathological phenomena which 
this condition presents. For it is plain that arsenicism, 

1 Bouchardat, Annuaire de Therapeut. de Matiere medic. Paris, 1879, p. 13. 

2 Mattison, Schmidt's Jahrbiicher, 1875, No. i., p. 21. 

3 Lahr, Zeitschr. f. Psychiatrie, 1872, H. 3. 

4 Fiedler, Deutsche Zeitschr. f. pr. Medicin, 1874, No. 27. 

5 L. Lewin, eod. loco, 1874, No. 28. 

6 Levinstein, Die Morphiumsucht, berlin, 1876, and Berl. klin. Wochenschr., 
1875, No. 48. 

1 Burkart, Die chron. Morphiumvergiftung, etc. Bonn, 1877. 
IO 



I4 6 INCIDENTAL EFFECTS OF DRUGS. 

alcoholism, the saturnine affections, and others, conditions 
in which the mental and bodily attributes are seriously 
and extensively disordered, can be regarded from a clini- 
cal stand-point only as intoxications, each of which has 
received a special stamp only because a series of second- 
ary phenomena have rendered the pathological picture 
more complicated, in consequence of the long duration of 
the condition. 

The treatment of opium-eating and the morphine-habit 
consists, of course, in the withholding of the particular 
drug. Opinions differ as to the manner in which this 
should be done, whether suddenly or gradually. The 
discussion of this question, as regards pure opium, was 
already carried on at a time when the morphine-habit was 
still unknown. Christison first practised the sudden with- 
drawal of the drug, in the year 1850. According to 
Flemming (1. a), the mental and physical sufferings of the 
patient are much increased by this method of treatment. 
He becomes sleepless, irritable, anxious, despairing, and 
begs and prays for opium. With this condition are asso- 
ciated thirst, neuralgic pains, diarrhoea, sweating, attacks 
of chilliness, etc. But, on the other hand, the sudden 
stoppage of the drug puts the moral and physical powers 
of the patient to a less severe test than the method of 
gradual diminution of the quantity taken, in which the 
same unpleasant reaction takes place at every dose, no 
matter how small it may be. In recent times both meth- 
ods have found defenders, as regards the morphine-habit 
also. During the course of the withdrawal, when the 
patient is completely isolated, and has no opportunity to 
procure the drug for himself, there frequently occur con- 
ditions of collapse, for counteracting which stimulants 
must be freely employed, since otherwise a fatal result 
may easily take place. Just as much to be dreaded are 
the conditions of excitement which appear soon after the 



NARCOTICS. 



47 



withdrawal of the morphia, in which attempts at suicide 
are by no means uncommon. To determine whether, 
•during- the withdrawal, morphia has been secretly admin- 
istered, nothing- can be done except to study the subjective 
condition of the patient. If this be very good, a suspicion 
that such is the case would be justifiable. The demon- 
stration of the presence of the alkaloid in the urine gener- 
ally fails, since it rapidly decomposes in the blood, as 
Landsberg 1 has shown. 

Only a very insignificant minority of these patients 
succeed in really and permanently weaning themselves 
from the drug. The large majority fall back again into 
the old vicious habit sooner or later after the withdrawal. 
The employment of substitutes for morphia, such as can- 
nabis indica, hyoscyamus, etc.. is attended with no practi- 
cal benefit. The use of atropia, valerianate of zinc, qui- 
nine, and bromide of potassium as symptomatic remedies 
is not indicated, because as long as the exciting cause is at 
work, the temporary relief of this or that pathological 
phenomenon is of no practical value. 

Cannabis Indica. 

In accordance with the good quality of the preparation 
and the individuality of the patient, unexpected results of 
varying intensity appear after the use of the preparations 
of hemp. Unlike the phenomena produced by the inges- 
tion of opium, these are relatively rare and speedily pass 
away, leaving no unpleasant after-effects. A number of 
observations bearing upon this subject were communi- 
cated by Schroff. 2 He generally noticed in those upon 
whom he experimented, a blunting of the tactile sensi- 
bility, a feeling as if the lower extremities were asleep, 
dizziness, visual hallucinations, and slight delirium. 

1 Landsberg, Pfluger's Archiv, Bd. xxiii., 1880, p. 432. 

2 v. Schroff: Lehrbuch der Pharmakologie, 1855, p. 536. 



T4 8 INCIDENTAL EFFECTS OF DRUGS. 

Husemann, 1 in experimenting upon himself, once pro- 
duced a condition of tearful joyfulness, while, on another 
occasion, his mental condition was sorrowful — a state 
which was in exact correspondence with the hallucina- 
tions and illusions which he experienced at the time. 

Caffeinum. 

Caffe'in, which is so much used in the treatment of 
migraine, seems to produce different effects upon different 
persons. Husemann, 2 who took only 0.24 gram (gr. iv.), 
afterwards observed intense congestion of the head and 
difficulty of respiration; while Albers, 3 after 0.18-0.3 
gram (gr. iij.-v.) of the citrate of caffeiin, felt no effects 
whatever ; and Frerichs, even after two grams ( 3 ss.) of 
pure caffeiin, noticed only congestion of the head and one 
attack of vomiting. 

Folia Hyoscyami— Extr. Hyoscyami. 

The incidental effects which show themselves after the 
use of preparations of henbane correspond in many re- 
spects to those produced by belladonna. The first, as 
regards importance, is an affection of the skin, which pre- 
sents itself in many persons as an erythema. Thus, Cabot 4 
describes the case of a man who took tincture of hyoscy- 
amus to relieve pains in the abdomen. A short time 
afterwards, his nose began to swell, and gradually the 
whole body became similarly affected, and the seat of 
itching and burning. The face was red and shining, and 
the redness gradually spread as far as the umbilicus, below 
which there appeared only isolated red patches. This 

1 Husemann: Handbuch der Toxikologie, 1862, p. 430. 

2 Husemann, 1. c, p. 544. 

3 Albers, Deutsche Klinik, 1853, 34. 

4 Cabot, Amer. Jour, of Med. Sciences, Oct., 1851. 



NARCOTICS. I49 

erythema began to grow paler an hour and a half later, 
and had entirely disappeared by the second day. Bes- 
sieres, 1 in the case of a lady who was accustomed to use 
vaginal injections of a decoction of hyoscyamus, also 
observed an erythema on the face after she used the same 
preparation per enema. Picard 2 also reports the case of 
a woman who, after an injection into the rectum of a 
medicinal dose of hyoscyamus, was attacked by an intense 
erythema of the face. 

Golding 3 saw a pustular eruption several times after 
the repeated internal use of small doses of henbane. 

Functional disturbances in other organs may appear 
simultaneously with this affection. In this category belong 
an excessive dilatation of the pupils, a feeling of dizziness, 
weakness, and collapse. Paralytic conditions of the upper 
and lower extremities have been also occasionally ob- 
served. If the use of the drug be persisted in, it is said 
that swelling of the parotids, salivation, and catarrhal 
inflammation of the nasal mucous membrane may also 
occur. 

Therapeutical interference is necessary only on the 
appearance of symptoms of weakness, in which case stimu- 
lants should be administered. 

Atropia. 

Atropice Sulphas. 

Daring the external employment in ophthalmological 
practice of atropia in the ordinary doses, there appear in 
some persons, in addition to its physiological mydriatic 
effect, certain abnormal local and general symptoms, due 
to the absorption of the agent. 

1 Bessieres: Abeille medicale, Novembre, 1853. 

2 licard, Ref. in Fodere: Traite de Medec. lega^ et d'hygiene publ , T. iv., 
P- 25. 

3 Golding, in Wibmer: Wirkungen der Arzneimittel und Gifte. Munch en, 
1842, Bd iii , p. 1219. 



150 



INCIDENTAL EFFECTS OF DRUGS. 



As regards the local phenomena, v. Graefe 1 made the 
observation that the at first unirritating mydriatic could 
not be long borne by some individuals. " An anatomical 
change is produced, as a result of the repeated action of 
the agent, which modifies the normal susceptibility of the 
conjunctiva to further medicinal influences. When the 
membrane is once saturated with atropia, there therefore 
occurs, after each new instillation, blepharo-conjunctival 
irritation, lachrymation, oedema of the lids, and even 
eczematous eruptions. This antipathy of the conjunctiva 
to atropia sometimes persists for months after the suspen- 
sion of its use, during which time the mucous membrane 
may present an entirely normal appearance. In the most 
pronounced cases, granulations of a peculiar kind appear,, 
somewhat similar to the ordinary vesicular lymph-follicles 
of the lower lid, and only distinguishable from them by 
their somewhat more consistent and more yellowish con- 
tents, and the altered condition of the vascular supply of 
the mucous membrane." Graefe recommends, in order to 
be able to employ atropia again in such cases, the inter- 
mittent use of solutions of the acetate of lead or nitrate of 
silver. 

In addition to these local changes, Graefe 2 sometimes 
noticed permanent dilatation of the pupils, after the use of 
atropia, particularly in cases of syphilitic iritis. 

The symptoms due to absorption of the agent, which 
occur after its application to the eye, point to a central 
action of atropia, such as ordinarily occurs only in cases of 
poisoning by it. They are, as a rule, but rarely observed 
after instillation of atropia or the use of collyria containing 
it, and are not dependent upon the quantity of the drug 
absorbed by the eye, but are due to the action of that 
portion which is taken up by the lachrymal ducts, and 

1 v. Graefe, Archiv f. Ophthalmol., Bd i., 2, p. 242, and Bd. x., 2, p. 200. 

2 v. Graefe, eod. loco, Bd. ii. 



NARCOTICS. 



5 



reaches the throat and stomach. Susceptibility to this 
mode of action of atropia stands, therefore, in direct pro- 
portion to the width of the tear-passages. Proof of this 
statement is furnished, according to R. Liebreich, 1 by 
those who have impermeable tear-ducts, whose general 
condition is never affected by even the largest doses, used 
for a long period. According to an observation of Chas- 
saignac, in a case of double cataract with adhesions of the 
iris to the capsule, in which three or four drops of a solu- 
tion of atropia (0.06 gram to ten grams of water; gr. i.- 
fl. 3 iiss.) were instilled into the eye, there occurred in 
thirty minutes dizziness, and later, turgescence of the face, 
tickling in the throat, and hallucinations of the senses. 
These symptoms disappeared spontaneously three or four 
days later. Laborde 2 saw fulness of the head and marked 
delirium occur after its use by adults, while Galezowski 
observed convulsive phenomena in children only. 

This statement of Laborde finds interesting confirmation 
in an observation of Kowalewski. 3 After the application 
of a considerable quantity of atropia to the eye of a man, 
there appeared great excitement as well as hallucinations 
of hearing, sight, and feeling, which the patient described 
as the embodiment of abstract ideas. On the fifth day, 
dryness of the mouth, spasm of the throat, etc., also 
appeared, and complete recovery took place only after 
ten days. 

Especially worthy of notice in this connection is an 
observation of v. Graefe, 4 that in consequence of the pro- 
longed use of atropin collyria, there not infrequently 
occur symptoms which are recognizable as erethisti'c 
weakness and interruption of assimilation. It is difficult 

1 R. Liebreich, Berl. klin. Wochenschr., 1864, p. 457. 

2 Laborde, Gazette medicale de Paris, 1878, p. 606. 

3 Kowalewski, Allgemeine Zeitsch f. Psychiatrie, Bd. 36. Heft 4. 

4 v. Graefe, Archiv f. Ophthalmologic, Bd. ix., 1864. 



15: 



INCIDENTAL EFFECTS OF DRUGS. 



to recognize this condition and refer it to its real cause, on 
account of the fact that other symptoms of the action of 
atropia are lacking. 

It is unnecessary to attempt curative treatment of 
these affections, because the above-described symptoms 
usually cease soon after suspending the use of the drug. 
If they become very urgent, small doses of morphia 
should be administered (0.005-0.01 gram — gr. -^— J-). 
Prophylactic measures are, however, indicated. Accord- 
ing to the advice of R. Liebreich (1. c), patients should be 
recommended to bend the head forwards during instilla- 
tion of atropia, not to swallow the tears or the fluid which 
drops from the eyes, to blow their noses frequently, and 
to gargle, or to press a finger into the corner of the eye 
and draw the tear-duct downwards. Since this manoeuvre 
does not always succeed, when the patient is awkward or 
in a reclining position, Liebreich employs a small forceps 
similar to a serre-fme, with which the lid at the angle of 
the eye is grasped in such a manner as to produce a 
slight degree of ectropium, and tarn the puncta lachry- 
malia downwards and outwards. It usually suffices to 
treat only the lower lid in this manner; when large doses 
are used, and in the cases of sensitive persons, the upper 
lid must also be included. 

Incidental effects are more rarely observed after the 
internal administration of atropia. When they do appear, 
they are generally limited to dryness of the mouth, a 
feeling of rawness in the throat, slight fulness of the 
head, the appearance of rings before the eyes, and some- 
times diplopia, and redness of the face. Only after large 
doses do threatening symptoms show themselves, on the 
part of the circulatory system, the motor and psychical 
spheres, and the general sensibility. 

An affection of the skin is occasionally observed after 



NARCOTICS. 153 

small medicinal doses. Thus Lusanna 1 reports a case, in 
which fifteen minutes after taking a small dose of atropia 
the skin became intensely red, and presented the appear- 
ance of having been exposed to the intense heat of the 
sun. This erythema lasted from one-half to one hour, and 
appeared every time the drug was taken. 

Belladonna. 
Folia — Radix — Extr actum — Unguentum Belladonna?. 

After the external or internal employment of bella- 
donna, various authors have observed an exanthema, 
which, like most drug-eruptions, is of a very transitory 
nature. The affection is sometimes general and some- 
times localized, and appears, as Guerard 2 states, especially 
in children, even after very small doses. Tt usually as- 
sumes the form of extensive erythematous patches, or a 
scarlatinous exanthema. The spots disappear on pres- 
sure, but return immediately when this is removed. They 
affect, by preference, the face and neck, and appear with- 
out itching, and speedily pass away. They may show 
themselves a very short time after the administration of 
the drug, and may pass through the various stages of 
development in a few hours. In some cases, as if to ren- 
der perfect the apparent likeness to scarlatina, there follow 
redness and painful swelling of the throat. Fever is not 
present, and no desquamation occurs. 

Traube 3 gives it as a result of his experience that such 
an eruption may occur after taking belladonna. Beren- 
guier 4 observed a diffuse scarlatinous redness, which ap- 

1 Lusanna, L' Union me'dicale, 1854. 

2 Guerard: Des eruptions medicamenteuses pathogenetiques. Paris, 1S62, p. 
26. 

3 Traube : Beitrage zur Pathologie und Physiologic Berlin, 1871, ii., Abth. 
1, p. 163. 

4 Berenguier, 1. c, p. 31. 



154 INCIDENTAL EFFECTS OF DRUGS. 

peared after taking a mixture containing belladonna, 
lasted eight hours, and then suddenly disappeared. In 
the cases of two lying-in women, who had used for several 
days a belladonna liniment, to relieve swelling of the 
mammary glands, Wilson 1 witnessed the occurrence of a 
scarlatina-like exanthema, which disappeared without des- 
quamation after three or four days. Kobner 2 also found 
well-marked hyperaemia, particularly of the face, after the 
introduction into the vagina of a suppository containing 
extract of belladonna. 

It will be readily understood from what has been said 
about atropia, that belladonna, after its external or inter- 
nal use, may also excite other abnormal somatic symptoms 
which are identical with the phenomena produced by the 
action of atropia. Two cases reported by Golden 8 are 
worthy of notice, in which the inunction of belladonna 
ointment upon the breast suppressed the secretion of milk. 

. DUBOISINUM. 

Duboisia is the yellow alkaloid, in the form of an extract, 
prepared by Gerrard, and at the same time by Petit (1878) 
from a plant which grows in Australia, the Duboisia myo- 
poroides, belonging to the family of Solanaceae. It is 
sparingly soluble in water (1 : 120) but dissolves readily in 
alcohol, chloroform, etc. The watery solution has a 
slightly alkaline reaction. Its sulphuric acid compound is 
crystalline. 

The main effect of duboisia is to produce dilatation of 
the pupils, in which respect it equals atropia, or even far 
surpasses it, as some investigators found. Wecker 4 states 
that it is less irritating to the conjunctiva than atropia. A 

1 Wi'son, Virchow-Hirsch's Jahresbericht f. d. ges. Medicin, 1872, i., p. 380. 

2 Kobner, Berl. klin. Wochensch., 1877, p. 328. 

3 Golden, Lancet, 1856, No. 6. 

4 Wecker, Bulletin de Therapeutique, 1879. 



NARCOTICS. 



55 



solution of o.ooi gram (gr. -fa) in water, subcutaneously 
injected, prevents or lessens the colliquative night-sweats 
of phthisical patients. 

Gubler, on the other hand, after the subcutaneous injec- 
tion of 0.0005 gram (gr. y^) of this substance, observed 
dryness of the throat and visual disturbances, and after 
0.001 gram (gr. ^l), thirst, increased frequency of the pulse, 
redness of the skin, and sometimes collapse. Sidney Rin- 
ger found that three drops of a solution of duboisia 1 : 4 
parts of water, subcutaneously injected at the height of 
the action of pilocarpin, made the skin perfectly dry 
in seven minutes, and after ten minutes produced such a 
sensation of dryness in the mouth that the patient com- 
plained of it. 

Incidental effects have already been observed after the 
external application of this drug to the eye also. Thus 
Davidson 1 reports eight cases, in which, after the instilla- 
tion of duboisia into the conjunctival sac, pathological 
symptoms of varying intensity appeared, such as dizziness, 
restlessness, and excitement increasing to violent delirium. 
Dryness of the throat was also observed in some cases. 
Scholer 2 used the sulphate in a solution of 0.05 : 5.0 (gr. f : 
lxxv.) without producing symptoms of general intoxication. 
On the other hand, in three or four cases, after the em- 
ployment of this agent, he observed a well-marked con- 
junctivitis follicularis, and in two or three cases pain 
during the instillation, redness of the conjunctiva, and 
failure of the effect upon the pupils. 

ACONITIA. 

Tuber a — Extract. — Tinct. A coniti. 

The effects of the different kinds of aconitia prove that 
the mode of preparation of the alkaloids is capable of 

1 Davidson, Lancet, September 6th, 1879. 

2 Scholer, Jahresbericht iiber s Augenklinik fur 1878. Berlin, 1879. 



1 56 INCIDENTAL EFFECTS OF DRUGS. 

modifying- their action. While German aconitia is by no 
means to be regarded as relatively one of the most poison- 
ous of substances, this claim is made by nearly all English 
experimenters for English aconitia (Morson's napelline or 
pure aconitine) which is probably prepared by a secret 
process from Aconitum ferox. 

While the largest permissible dose of German aconitia, 
according to the Pharmacopcea Germanica, is 0.004 gram, 
(gr. -J^.), Pereira 1 saw almost fatal consequences ensue from 
the use of 0.0015 gram (gr. -fo) of English aconitia. Al- 
though it is true that the individuality of the persons using 
these powerful agents plays a certain role, the differences 
in the mode of action of the two kinds of aconitia, which 
have been demonstrated by Schroff also, are too great to 
be left out of consideration by physicians in their observa- 
tions of the injurious incidental effects of the drug, such 
as have been observed in different degrees after both 
preparations. 

According to Pereira, English aconitia, even in very 
small doses, produces a sensation of heat and itching on 
the surface of the body. After its external employment, 
Turnbull 2 observed pricking, of the parts to which it was 
applied, and Schroff, 3 after painting a weak alcoholic solu- 
tion of this aconitia upon the forearm, experienced prick- 
ing and formication, without the appearance of inflamma- 
tory changes. 

Cases of poisoning, which occurred in consequence «of 
the administration of English instead of German aconitia, 
are frequently met with in literature. The English prep- 
aration should, in our opinion, be entirely abandoned for 
internal use. 



1 Pereira, Refer, in Husemann, Pflanzenstoffe, i87i,p. 226. 

2 Turnbull, Refer, in Husemann, Pflanzenstoffe, 1871, p. 226. 

3 Schroff, Jour. f. Pharmakodynamik, Toxikologie und Therapie, Bd. i., 1857, 
P- 365. 



NARCOTICS. 157 

German aconitia and the other pharmaceutical prepara- 
tions made from the Wolfsbane, cause, as Dworzak and 
Heinrich 1 found in their own cases, a biting, burning feel- 
ing upon the lips and tongue, and salivation. An eruption 
of white vesicles has also been occasionally observed on 
these parts. A vague drawing sensation in the face also 
occurs not infrequently, which may pass into a persistent 
pain involving the distribution of the trigeminal nerve, 
and be accompanied by an intensely annoying feeling of 
pricking, usually on the chin and cheeks, but also appear- 
ing on the body and extremities. The gastric and intesti- 
nal mucous membranes are also irritated by this drug. 
Nausea occurs, and even vomiting and rumbling in the 
abdomen. If the use of the aconite be continued, more 
remote effects are produced, such as headaches, more or 
less intense fulness of the head, buzzing in the ears, and 
general weakness, symptoms which disappear a short time 
after the administration of the agent is suspended. 

Although as a rule no symptoms which threaten life are 
to be expected from the use of medicinal doses of German 
and other preparations of aconitia, direct therapeutical 
interference may become necessary when cardiac lesions 
or other causes predisposing to a more intense action of 
the drug are present. Contrary to the view formerly 
entertained, it has been shown by L. Lewin 2 that aconitia 
belongs to that class of cardiac poisons whose fatal action 
may be long deferred, or even absolutely prevented, by 
long-continued artificial respiration. This procedure must 
therefore be- resorted to whenever symptoms of dyspnoea 
and anomalous heart-action (interruption and irregularity 
of rhythm) show themselves. When milder effects of 
aconitia appear, the usual stimulants and diuretics may 

1 Dworzak u. Heinrich, Prager Vierteljahr. , Bd. 42, p. 153, et seq 

2 L. Lewin: Experimentelle Untersuchungen uber die Wirkung d. Aconitin 
auf d. Herz. Berlin, 1870. 



l$% INCIDENTAL EFFECTS OF DRUGS. 

also be employed to produce a more rapid elimination of 
the drug. No direct antidote for aconitia is known. 

Veratria. 

Rhizoma — Tinct. Veratri. 

The alkaloid prepared from white hellebore as well as 
the roots of the plant produce not infrequently, when 
used therapeutically, a few pathological phenomena which 
were known even to physicians of the middle ages. They 
may occur with more or less intensity after any mode of 
administration of the drug. 

A mere trace of the powder, accidentally brought in 
contact with the nasal mucous membrane, causes violent 
sneezing lasting for a considerable period, which may re- 
sult in profuse epistaxis. The conjunctiva is affected with 
equal violence when veratria in solution or in the form of 
an ointment is applied to it. The relatively extensive ex- 
ternal use of this agent in the treatment of neuralgias of 
various nerve-tracts has furnished abundant opportunity 
for becoming familiar with the symptoms which it pro- 
duces. An ointment of 0.6-1.0 gram (gr. x.-xv.) of ve- 
ratria, thirty grams ( 1 i.) of simple cerate, soon produces 
prickling and a feeling of increased heat, not only at the 
point of application, but also on remote parts of the body. 
This sensation, according to Reiche, 1 gradually increases to 
burning, and if the application be long continued, a feeling 
of restlessness and anxiety appears. These phenomena 
may become permanent, if the use of the drug be not dis- 
continued, and deprive the patient of sleep. An itching 
petechial or vesicular eruption, which soon disappears 
after the use of the drug is stopped, is occasionally ob- 
served on different parts of the body. 

More intense incidental effects may be produced by the 

1 Reiche, Medic. Zeitung d. Vereins f. Heilkunde, 1839, 23. 



NARCOTICS. 159 

internal use of the drug. Owing to its power of reducing 
the frequency of the pulse, the blood-pressure and the 
temperature, and of slowing the respiration, veratria was 
and is still employed in acute febrile affections, particu- 
larly in pneumonia. In such cases, it is usually adminis- 
tered several times daily, in doses of from 0.003-0.0005 
gram (gr. ^V~rio)' an( ^ even beyond the maximal limit of 
0.01 gram (gr. £). But even the small normal doses usu- 
ally excite dryness in the mouth, burning thirst, difficulty 
in swallowing, nausea, choking, and vomiting, and some- 
times also salivation, colicky pains, and diarrhoea, in which 
the stools may be tinged with blood. Children often 
vomit, as Forcke 1 states, even after the first dose, adults 
more rarely. 

During the prolonged use of medicinal doses of the 
drug, there occurs a pricking or burning feeling on 
remote parts of the body, particularly the extremities. 
In some individuals there appear dizziness and dimness of 
sight, and also trembling and unsteadiness of gait. In 
others, well-marked collapse may take place. Cerebral 
symptoms occur not infrequently in children after the 
administration of tincture of veratrum viride. Thus, 
Fleischmann 2 reports that, after the hourly administration 
to a boy of a teaspoonful of the following mixture : Tinct. 
Veratri virid. gtt. vi., Mucilag. acac. 60 grams (fl. § ij.), 
there appeared dryness of the throat, great thirst, and, 
after a while, convulsive movements of the hands and 
fingers lasting but a short time, foolish talking, and mild 
delirium. 

Forcke, in a few cases, saw a pustular eruption on the 
face, most marked around the mouth. 

After the subcutaneous injection of the drug in alcoholic 

1 Forcke: Physiologisch-therapeutische Untersuchungen iiber d. Veratrin. 
Hannover, 1837. 

2 Fleischmann, Prager medic. Wochenschr. , 1876, No. 10. 



l6o INCIDENTAL EFFECTS OF DRUGS. 

solution, in doses of o.ooi 2-0.001 5 gram (gr. gL— ^), Eulen- 
burg * witnessed the formation of an abscess in one case, 
and usually the appearance around the point of puncture 
of a slight, sometimes spotted, redness and swelling. The 
feeling of burning lasted several hours after the injection. 
Hiffelsheim also noticed pain and erythema after the hypo- 
dermic use of veratria. Sometimes the toxic action was so 
much intensified as to lead to prostration. 

The treatment of these incidental effects, besides the 
immediate suspension of the use of the drug, should con- 
sist in the administration of analeptic substances, particu- 
larly the aromatic spirits of ammonia, in*twenty to sixty 
drop doses, 2 or, according to Reiche, of black coffee with 
lemon juice. In cases where gastric catarrh is present, the 
drug, according to Trotzscher, 3 should never be prescribed. 

EXTRACTUM FAB.E CALABARIOE. 

Eserina s. Physostigmia. 

The incidental effects which show themselves after the 
application of preparations of Calabar bean to the eye 
have been clearly described in the classical investigations 
of A. v. Graefe. 4 According to this author, the drug 
passes through the cornea, is dissolved in the fluids 
of the eye, and acts directly upon the iris and ciliary 
muscle. He found that immediately after the instillation 
of a solution of the alcoholic extract in glycerin, there 
appeared an itching feeling in the conjunctival sac, with a 
corresponding reflex action upon the orbicularis muscle 
and the lachrymal secretion, varying in degree with the in- 
dividuality of the patient and the concentration of the pre- 
paration employed. Afterwards, when the contraction of 

1 Eulenburg: Die hypodermatischen Injectionen. Berlin, 1875, p. 278. 

2 Husemann: Pflanzenstoffe. Berlin, 1871, p. 510. 

3 Trotscher: Wiener Medicin. Halle, 1863, p. 487. 

4 A. v. Graefe, Archiv f. Ophthalmologic, Bd. ix., 1863, III., p. 87. 



NARCOTICS. l6i 

the pupil and the accommodative changes begin, the sub- 
jects of experiment complain of a painful tense sensation, 
partly along the equator of the globe, and partly in front 
of it, in the region of the ciliary body. Other observers 
describe a nervous aching pain in the whole globe, which 
may, after the manner of ciliary neuroses, spread along 
the supraorbital nerves, and, like migraine, may extend 
over the corresponding side of the head. Graefe leaves it 
undecided whether spasm of the tensor or of the sphincter 
is more involved in the production of these pains. 

He failed to observe any more remote effects. If such 
should appear, they would be most easily explained by the 
passage of the drug along the tear-ducts. 

After the administration of small doses of the extract of 
Calabar bean, as it is sometimes employed in the treat- 
ment of neuralgias, tetanus, and epilepsy, and also in cases 
of poisoning by atropia and strychnia, Fraser 1 noticed a 
painful feeling in the epigastrium, as well as giddiness 
and weakness of the muscles of the extremities. The last 
symptom may pass into a condition resembling paralysis, 
which, however, lasts but a short time. 

After small doses of physostigmia, Leven 2 witnessed 
the occurrence of nausea and general discomfort. 

Amygdalae Amar^:. 

Aqua Amygdal. Amararum — Aqua Laurocerasi. 

Stille 3 states that bitter almonds, in medicinal doses, 
sometimes produce an abundant eruption resembling urti- 
caria. Gregory also noticed such an eruption upon him- 
self after eating a bitter almond. This effect is due to the 
presence of hydrocyanic acid in the almond, as is proven 



1 Fraser: Transactions of the Royal Society of Edinburgh, xxiv., 1867, 73. 

2 Leven, Jour, de Pharmac. et Chimie, I., 70. 

a Stille: Therapeutics and Materia Medica. Philadelphia, 1874, i-» P« I75« 



\§2 INCIDENTAL EFFECTS OF DRUGS. 

by the fact that solutions containing this acid, such as 
bitter-almond and cherry-laurel water, very easily pro- 
duce the same incidental effects. 

Small doses (ten drops) of cherry-laurel water may 
excite tickling in the throat and increased flow of saliva. 
If this dose be somewhat increased, as is so commonly 
done in practice, or if small doses be frequently repeated, 
nausea, vomiting, dizziness, and headache appear not 
infrequently, as Coullon 1 has stated. With the sensation 
of giddiness may be associated buzzing in the ears, diffi- 
culty of respiration, and great weakness. 

Upon the ground of these facts, and in view of the 
greatly varying strength of waters containing prussic acid, 
and also the great differences in the susceptibility of indi- 
viduals to the action of this agent, Kohler 2 justly protests 
against its employment in large doses as an antispasmodic, 
a practice usually regarded as devoid of danger. It has 
been best described by Trousseau and Pidoux, who said of 
it that it is often dangerous, nearly always useless, and 
very rarely beneficial. 

Semen Colchici. 

Tinctura — Vinum Colchici. 

The activity of the preparations of colchicum depends 
upon the proportion of colchicia which they contain. 
This, however, varies with the season in which the plant 
is gathered. According to Aschoff and Bley, 3 colchicum 
root is richest in colchicia during the months of July and 
August. It is not impossible that this circumstance is 
influential in determining the abnormal phenomena which 

1 Coullon : Recherches et considerat. medic, sur l'acide hydrocyan. Paris, 
1819. 

2 Kohler: Handbuch der physiolog. Therapeutik. Gottingen, 1876, p. 1233. 

3 Aschofl und Bley, Archiv d. Pharmacie, Januar, 1857. 



NARCOTICS. ^3 

sometimes follow the therapeutical employment of the 
drug. 

After small doses, 0.1-0.3 gram (gr. iss.-ivss.) of the 
seed, a burning sensation in the throat and stomach, ptya- 
lism, distressing nausea, and watery stools, with rectal 
tenesmus, are frequently observed. Some, or all these 
phenomena appear in some cases only after the long-con- 
tinued use of the agent, but, in others, they may occur 
soon after taking it. With them are not infrequently asso- 
ciated, but with greater rarity, a feeling of fulness of the 
head, dizziness, and headache. The secretion of urine 
may also be attended with pain. 

The symptoms which originate in the stomach, intes- 
tines, and kidneys should be regarded as the result of a 
local irritation set up by the drug. This statement is 
substantiated by the fact, which has been established tox- 
icologically, that, in both man and animals, intense inflam- 
matory changes in the mucous membranes of these organs 
may be found after large poisonous doses of this drug. 

The above-described incidental effects of colchicum are 
most frequently observed after the use of the wine of col- 
chicum seed, the dose of which is usually given as two 
gr,ams (fl. 3 ss.), or six grams (fl. 3 iss.) daily. This is cer- 
tainly too large, if the preparation is made from the fresh 
active plant. 

The action on man of colchicia (which is officinal in the 
Pharmacopoeia Austriaca) has been studied by Schroff. 2 
After taking 0.0 1 gram (gr. ■$•), there appeared at first a 
bitter taste, later, a tickling sensation in the mouth, and 
soon afterwards eructation, nausea, inclination to vomit, 
and salivation. After 0.02 gram (gr. -J), besides these 
symptoms, vomiting and diarrhoea occurred, with tenes- 
mus, and also a feeling of chilliness, and sleeplessness. 

1 Monneret, Archive ge'ner. de Medecine, 1844. 

2 Schroff, Oesterreich. Zeitschr. f. pr. Heilkunde, 1856 ii., 22. 



^4 incidental effects of drugs. 

Folia Digitalis. 

Extr actum — Tinctura — Infusum Digitalis. 

Digitalis, in common with only a small number of other 
drugs, possesses the peculiar faculty (which is probably 
due solely to an unusually slow elimination through the 
kidneys) of unfolding its action in the body during a rela- 
tively long period, and, therefore, of developing cumula- 
tive effects when repeated doses are administered. These 
may, under certain circumstances, produce threatening 
phenomena, or even symptoms of poisoning, among which 
are headache, dryness of the throat, nausea, and a sensa- 
tion of choking, and, in well-marked cases, buzzing in the 
ears, disturbances of vision (manifested by the appear- 
ance of sparks before the eyes, amblyopia, or diplopia), 
also dizziness, swooning, vomiting, diarrhoea, sleeplessness, 
a thready, scarcely appreciable, and sometimes arhyth- 
mical pulse, and a very great fall in the bodily tempera- 
ture, a result of the slowing of the circulation. A headache, 
which appeared after even 0.03 to 0.09 gram (gr. ss.-iss.) 
was a prominent symptom in many cases. In a large 
number of patients, even 0.15 gram (gtt. iij.) of the tinc- 
ture sufficed to produce the above-mentioned phenomena. 
In the absence of a true antidote for digitalis, the treat- 
ment of these symptoms consists in the administration of 
symptomatic remedies, stimulants, irritants to the skin, 
etc. From a prophylactic stand-point, special attention 
should be paid to the cumulative power of the drug, 
which may sometimes cause sudden death from paralysis 
of the heart, particularly when the agent is to be taken 
for some time, and its use must be stopped on the first 
appearance of abnormal subjective symptoms. 

An observation of Traube 1 on an affection of the skin 

1 Traube, Charite-Annalen, Jah-g. i., p. 622 u. Jahrg. ii., p. 19. Beitrage zur 
Pathologie u. Physiologie, Bd. ii., I. Abth., pp. 130, 136, 164. 



NARCOTICS. 165 

after the use of digitalis, should be mentioned as a very 
rare occurrence. In a case of pleuritis and pericarditis, 
the patient took, from the fourth to the sixth day of his 
illness, 3.75 grams (gr. lvii.) of digitalis in an infusion. 
Four days after the last dose,, there appeared, while the 
bodily temperature was normal, an erysipelatoid affection 
of the face, which resulted, five days later, in an excessive 
ragged desquamation. In a second case of pleuro-pneu- 
monia, 4.08 gram (gr. lxi.) of digitalis were taken in five 
days in the form of an infusion. Four days after taking 
the last dose, the patient, who had hitherto been free from 
fever, experienced a rise in temperature, and, on the fifth 
day, there appeared on the body, the supinator surfaces 
of the forearms, and the backs of the hands, a papular ex- 
anthema, made up of quite prominent, carmine-red, round- 
ed spots, disappearing on pressure, the majority of which 
united to form large patches elevated above the surface 
of the skin. On the next day, desquamation began on the 
face in tolerably large masses, while new eruptions showed 
themselves on the upper arms and neck. Four days later 
still, the exanthema had almost entirely disappeared, and 
not until some time afterwards, during the course of a 
newly-developed typhoid affection, did desquamation, in 
large flakes, occur on the body and extremities. 

A similar exanthema, spreading over the whole body, 
was observed by Schuchardt, 1 in the case of a young 
robust man who had taken digitalis for a long time for the 
relief of endocarditis. When the same patient took digi- 
talis again, one year later, the same eruption appeared 
with equal intensity. 

It is perhaps not unimportant, in order to facilitate the 
comprehension of the manner of occurrence of this affec- 
tion, to call attention to the fact that an ointment prepared 
from fresh digitalis leaves with lard may excite slight 

1 Schuchardt: Elandbuch der Arzneimittellehre. Braunschweig, 1858, p. 553. 



l66 INCIDENTAL EFFECTS OF DRUGS. 

inflammation and the eruption of a papular exanthema, 
when several times rubbed upon the healthy skin. More 
intense inflammation is produced upon the skin deprived 
of epidermis. In view of this fact, one can readily imagine 
that, when a certain individual disposition is present, the 
collection of a large quantity of the active principle of 
digitalis in the vascular channels may produce the same 
irritative effect upon the skin as the external application 
of the drug. This explanation is also supported by the 
fact that, in Traube's cases, the exanthema first appeared 
after the use of digitalis had been suspended. 

Worthy of notice is a statement of Reil, that cumula- 
tive effects are very rarely observed after the adminis- 
tration of digitalin, on account of the appearance of 
certain forerunners of intolerance of this agent, which 
often render its abandonment absolutely necessary. These 
are a sensation of weakness in the epigastrium, inclina- 
tion to vomit, exhaustion, dimness of vision, and heavi- 
ness of the head. 

Chloralum Hydratum Crystallisatum. 

The occurrence of incidental effects after the internal 
use of the hydrate of chloral is, in view of the very ex- 
tensive employment of the agent, by no means common. 
Even its habitual employment, which is very common, 
particularly in England and America, leads, as Richard- 
son 2 states, to no habituation of the drug, even in " chloral- 
drinkers," and produces no deleterious effects, as long as 
the permissible doses are not exceeded. Liebreich 3 has 
made the same statement upon the basis of reports from 
insane asylums, and has at the same time called attention 

1 Reil: Materia Medica der reinen Pflanzenstoffe. Berl ; n. 1857, p 155. 

2 Richardson, Medical Times and Gazette, February, 1871. 

3 Liebreich, Deutsche medic. Wochenschr., 1877, No. 27, und Berlin, klin. 
Wochenschr., 1874, p. 50. 



NARCOTICS. 167 

to the fact that, when a pure preparation is used to pro- 
duce an hypnotic effect, even during long periods, no in- 
crease in the dose is necessary, and that unpleasant effects 
are not observed, in which respects this drug differs from 
opium and its alkaloids. He also says that an impure 
chloral presents a constantly increasing acid reaction and 
exerts perverse therapeutic effects, in consequence of 
the formation of noxious chlorine compounds. 

The bad quality of the drug, which is usually the case 
with those preparations which are not well crystallized, 
is probably one of the causes of those cases of death after 
one or more medicinal doses, which are recorded in the 
literature of the subject. It is a significant fact, in this 
connection, that, during the early years of the employ- 
ment of chloral, many such cases were reported, while, on 
the other hand, in recent times, when improved methods 
of preparation have been employed, such accidents are 
very rarely described. When they do occur, it is natural 
to regard the impurity of the preparation used as their 
cause, particularly in view of the fact that we are familiar 
with several organic chlorine compounds which are cap- 
able of exerting deleterious effects, even in small doses. 
At the same time, individual predisposition to the occur- 
rence of such phenomena also plays a role, and the condi- 
tion of the absorbing organs should by no means be left 
out of consideration. 

It is characteristic of the cases of death after chloral, 
reported by various authors, that they occurred almost 
immediately or a short time after taking the drug, and 
usually during an attack of anxiety. Such cases have 
been reported, among others, by Notel, 1 after four grams 
( 3 i.) of chloral; Jolly, 2 of two insane persons after five 
grams (gr. lxxv.) each ; Marsh, 3 of four persons, the major- 

1 Notel, Virchow-Hirsch's Jahresbericht f. d. ges. Medicin, 1872, ii., p. 11. 

2 Jolly, Bair. arztl. Intelligenzblatt, 1872, No. 13, 14. 

3 Marsh, Virchow-Hirsch's Jahresb., 1875, 1., p. 479. 



l68 INCIDENTAL EFFECTS OF DRUGS. 

ity drunkards, after three grams (gr. xlv.), and Fiirstner, 1 
that of a girl, after two grams ( 3 ss.). The published 
results of autopsies give no information as to the causes 
of death. 

According to Kern,' 2 disturbances of the respiratory 
processes are excited in rare instances, which may increase 
from a feeling of anxiety, terror, and shortness of breath, 
to attacks of dyspnoea, and even asphyxia. Shaw 3 also, 
after about one gram (gr. xv.) of chloral, observed spas- 
modic breathing with irregular action of the heart. Marsh 
states that after an ordinary dose of chloral he has found 
changes in the mucous membrane of the respiratory appa- 
ratus, as shown by the occurrence of acute bronchitis. 

Much more common than the above-mentioned phenom- 
ena is the occurrence of conjunctival irritation after one or 
repeated doses of chloral. Redness and swelling of the 
membrane are observed, disappearing on the discontinuance 
of the administration of the drug. Steinheim 4 treated a 
lady suffering from asthmatic attacks, who on three occa- 
sions experienced a severe disorder of vision every time 
she took chloral. It appeared in the form of dimness of 
sight, or complete blindness. 

The condition described by Schiile 5 as chloral-rash y 
which is characterized by flashes of heat, and cerebral 
congestion with injection of the conjunctivas, occurs only 
when alcoholic beverages have been taken after the ad- 
ministration of chloral. 

Among other incidental effects, Curschmann 6 reported 
swelling of the epiglottis and false vocal cords, and Reimer 7 

1 Fiirstner, Arch. f. Psychiatric Bd. vi., 1876, p. 344. 

2 Kern, Allgem. Zeitschrift f. Psychiatrie, 1872, p. 316. 

3 Shaw, Virchow-Hirsch's Jahresber., 1871, i., p. 334. 

4 Steinheim, Berlin, klin. Wochenschr., 1875, p. 77. 

5 Schiile, Zeitschrift f. Psychiatrie, Bd. 28, p. 4. 

6 Curschmann, Deutsches Archiv f. kl. Medicin, Bd. viii., p. 151. 

7 Reimer, Zeitschrift f. Psychiatrie, Bd. 28, p. 316. 



NARCOTICS. 169 

the occurrence of decubitus. The ^etiological connection 
of the latter with the use of chloral is, however, very 
doubtful. According to Reimer, bed-sores produced by 
the use of chloral are distinguished from the ordinary 
variety caused by long-continued pressure, by the fact that 
the former develop under very slight external pressure, 
while the epidermis is still intact, and spread deep down 
into the subcutaneous cellular tissue. 

Here and there in the literature of chloral, cases are re- 
ported in which icterus is said to have occurred after the 
use of this agent. Thus Wernich 1 reports four observa- 
tions, in which, after the use of chloral, a pre-existing jaun- 
dice became intensified, and also the case of a drunkard, in 
which a fresh icterus appeared after four grams of hydrate 
of chloral were taken. Arndt 2 also witnessed the occur- 
rence of this condition in a paralytic, after he had taken 
the drug for fourteen days. The icterus passed off when 
the medicine was stopped, and reappeared when it was 
again used. Somewhat hazardous is an opinion of Gell- 
horn, 3 that, among others, atrophic affections of the liver 
of a very peculiar nature, may appear as the expression of 
an idiosyncratic action of chloral. This observation stands 
alone in literature. 

Besides the phenomena already cited, eruptions upon 
the skin, either polymorphous or simple, have been ob- 
served in some persons either immediately or some time 
after the use of chloral in varying doses. They may be 
classified as the erythematous, the urticaria-like, and the 
eczematous forms. 

I. The erythematous form is relatively the most common. 
In it the semblance of a diffuse hyperaemia is usually ob- 
served upon the face and neck. In other parts of the 

1 Wernich, Deutsches Archiv f. klin Medic, Bd. xii., p. 32. 

2 Arndt, Archiv f. Psychiatrie, Bd. iii., Heft 3. 
Gellhorn, Zeitschrift f. Psychiatrie, Bd. 28, p. 625. 



170 INCIDENTAL EFFECTS OF DRUGS. 

body, the erythema generally appears in the form of roseola- 
like or dark-red spots with irregular outlines, which bear 
a striking resemblance to purpura. According to Schulle 
(1. c), it seems to follow by preference the course of the 
larger nerve-trunks. It disappears when the use of the 
drug is suspended. In one case, Brown 1 observed an in- 
flammatory redness which spread uniformly over the 
whole body, while Husband, 2 in the case of a female patient, 
who for eight days took each day two doses of 1.3 gram 
(3t.) each, and for five days two doses daily of two grams 
each ( 3 ss.) each, witnessed the occurrence of a scarlatina- 
like exanthema, attended with high fever and increased 
sensitiveness of the skin, after the disappearance of which 
abundant desquamation occurred. Kobner 3 also reports 
a case in which, after the long-continued use of chloral, 
there appeared not a simple hyperaemic redness, but an 
erythema exsudativum which spread over nearly the 
whole of the body. It bore a very close resemblance to 
scarlatina, but the skin was much more swollen and infil- 
trated than in this disease. The eruption burned and 
itched, and, as the use of chloral was persisted in, ended in 
desquamation only after four or five weeks. 

II. The urticaria-like form has been observed by Gau- 
chet 4 and Chapman 5 among others. The latter saw it 
occur in the case of a lad) 7 ' who for fourteen days took one 
gram (gr. xv.) of chloral each evening. After this time an 
erythema showed itself, which passed off when the use of 
the drug was stopped, and when it was again administered 
wo days later, the skin over the whole body quickly be- 
came covered with wheals, and the seat of a feeling of 
heat. Hypersecretion of the conjunctivae appeared at 

1 Brown, Lancet, 1871, Vol. i., p. 440. 

2 Husband, eod. loco, 1871, No. 25. 

3 Kobner, Berl. klin. Wochenschrift, 1877, p. 327. 

4 Gaucher., Bulletin gener. de Therapeut., 1S71, p. 429. 

5 Chapman, Lancet, 1871. 



NARCOTICS. 171 

the same time. With this urticaria-like form must also be 
classed those eruptions which have been described as a 
papular exanthema, which appear under the same circum- 
stances. Thus Arndt (1. a), after the use of chloral for 
eight days, found a papular exanthema which covered at 
first the extensor surfaces of the upper extremities, and 
later the entire body. It came and went, in accordance 
with the use or abandonment of the drug. Kern (1. c.) ob- 
served a similar eruption located upon the arms. 

3. If the administration of the chloral be persisted in, 
the nodules may develop into vesicles with serous or puru- 
lent contents, and these, when they burst, may present a 
complete resemblance to eczema. This occurrence is, how- 
ever, very rare, and seems to be represented in literature 
by only one case, which was studied by Kern. This is, 
however, not a typical case, because during the existence 
of the eruption, quinine was administered hypodermically, 
a drug which is itself capable of producing a variety of 
dermatoses. On the person of a robust woman, the subject 
of puerperal mania, there appeared on the ninth day of 
the administration of chloral, an exanthema attended by 
fever, and at the same time swelling of the face, the cheeks, 
eyelids, and ears. After a while the eruption grew paler, 
but reappeared when chloral was again taken, and the 
skin now presented, in a widely-varying manner, the ap- 
pearance at one time of an impetiginous, at another of a 
moist, and at still another that of a squamous eczema or 
an ichthyosis, on account of the fact that the process of 
desquamation was not limited, as in the acute exanthemata, 
to a short period, but lasted for many weeks, during which 
time large masses of epidermis were cast off from all parts 
of the body. In a later period of the disease, the disturb- 
ances of the skin were marked by 'an extensive falling out 
of the hair of the head, and by a gradual casting-off of all 
the nails of the upper and lower extremities. 

Schiille and others regarded a paralysis of the vasomotor 



172 INCIDENTAL EFFECTS OF DRUGS. 

nerves, produced by chloral<as the direct cause of the af- 
fections of the skin. 

As in the case of other drugs, attempts have of course 
been made to explain the occurrence of the above-described 
incidental effects of chloral. Some authors regard them 
as the result of a chronic blood-poisoning, which is devel- 
oped only when the organism is saturated with the drug. 
If this be accepted, we must attribute a cumulative action 
to chloral, such as digitalis has already been shown to 
exercise. This hypothesis is, however, on a closer exam- 
ination of the conditions really present, shown to be un- 
tenable. By a blood-poisoning we understand such a 
chemical or physical alteration of the elements of the blood 
that they are no longer capable of performing their 
normal functions. In this sense one may speak of blood- 
poisoning by inhalation of carbonic oxide or sulphuretted 
hydrogen, by taking too large doses of chlorate of potas- 
sium, or by the entrance of any other heterogeneous sub- 
stances into the vascular channels. But in all these 
instances there occur changes. in the blood which can be 
objectively demonstrated, either by the spectroscope or 
the microscope, or even by inspection. No such mode of 
action has, however, been yet demonstrated for chloral, 
and we are, therefore, not justified in admitting the occur- 
rence of blood-poisoning in this instance. Neither can it 
be a certain definite degree of saturation of the organism 
with chloral which produces the incidental effects, for they 
show themselves, in some instances, even after one small 
dose. If, on the other hand, such a degree of saturation 
were really produced, a cumulative action of chloral would 
also occur, and this would suffice to maintain sedative or 
hypnotic effects for a long time, without further adminis- 
tration of the drug. That such is not the case requires no 
proof. Other factors must, therefore, co-operate in the 
production of the symptoms described. They are most 
naturally explained by the general facts already discussed 



NARCOTICS. 



173 



in the introduction to this work. It is probable that the 
chloral (or its products of decomposition) which reaches 
the different organs, exerts an irritant or a depressing 
action upon some persons, either in consequence of an ab- 
normal distribution of vessels, or of other individual pecu- 
liarities. These effects last as long as the products in 
question remain in the body. Their occurrence may also 
be facilitated by bodily conditions which cause a retarda- 
tion or an arrest of the elimination of waste material. 

No especial treatment is necessary for the relief of the 
above-described effects of chloral, since they disappear 
spontaneously on the discontinuance of the drug. The 
fever which usually attends chloral eruptions also requires 
no treatment, because quinine, as .Schiille states, has no 
effect, and cold baths are of slight utility. It must also be 
remembered, that, particularly in persons who possess a 
certain disposition to the occurrence of drug-eruptions, the 
administration of quinine may easily induce a variety of 
complications, so that it is on the whole better to abstain 
from its use. 

Chloroformum. 

Soon after the introduction of chloroform into medical 
practice, and in the midst of its progress through the 
civilized world, cases were made public in which persons, 
while under its influence, did not awake from their anaes- 
thetic sleep. Although in the beginning of the employ- 
ment of this agent, the reluctance to publish cases which 
ended in death could be explained by the circumstance 
that physicians, under whose care they occurred, attrib- 
uted them to their own want of skill, the increasing number 
of such accidents soon made it seem probable that there 
must be certain definite factors which should be regarded 
as the causes of the so-called " chloroform deaths." Up 
to the present time, however, these have not been defi- 
nitely determined, in spite of a very large number of 



1^4 INCIDENTAL EFFECTS OF DRUGS. 

most careful clinical and experimental investigations. The 
symptomatic phenomena, on the other hand, which attend 
or precede death from chloroform, have been carefully 
studied and accurately described. 

No warning prodromal symptoms precede the appear- 
ance of death in the minority of cases of fatal chloroform 
narcosis. The pulse stops suddenly, in either complete or 
incomplete anaesthesia, respiration ceases one or two min- 
utes later, the face becomes pale, the pupils dilate, and 
the patient dies; but, as a rule, the fatal termination of an 
anaesthesia is indicated by one or two, or a series of pre- 
monitory symptoms. There occur obstinate vomiting, a 
striking pallor of the face, labored, sometimes stertorous 
breathing, excessive dilatation of the pupils, absence of 
reflex movement on touching the conjunctiva, spasmodic 
muscular movements, a certain rigidity of the muscles, 
and a small, almost imperceptible or irregular pulse, which 
entirely ceases in some cases, in spite of the continuance 
of the action of the heart. Respiration stops either before 
or simultaneously with the arrest of the pulse, or contin- 
ues for a short while afterwards. In the former case, we 
recognize a death from chloroform by asphyxia, in the 
latter by syncope. Billroth 1 observed, just before a death 
from chloroform attended with convulsions, that a pre- 
viously bleeding wound of a finger ceased to bleed. 

Kappeler 2 has collected with great care the statistical 
data bearing upon death from chloroform, as far as they 
have been published. He reports one hundred cases, of 
which seventy-eight were of the male and twenty-two of 
the female sex. The highest mortality occurred between 
the ages of forty-six and sixty years, or 24.7 per cent. Next 
came the ages from thirty-one to forty-five years, with 



1 Billroth, Wiener medic. Wochenschrift, 1868, No. 46. 

2 Kappeler, Anasthetlka, Deutsche Chirurgie von Billroth und Lucke, Lief. 
20, p. 100 u. ff. 



NARCOTICS. 175 

20.7 per cent, while under five, only two, and over sixty,, 
only one death occurred. The patients died before com- 
plete anaesthesia in forty-three cases, and during it in 
forty-seven. In eleven cases, no statement was made as 
to this point. In fifty-six fatal cases of anaesthesia, the 
inhalation was practised by means of cloth or lint, in five 
cases with Esmarch's chloroform-basket, and, in the same 
number, with Clover's inhaling apparatus. The quantity 
of chloroform used varied in forty-six cases between 
twenty drops and thirty to sixty grams (fl. 3 i.-ij.), the 
average quantity being 11.1 grams (fl. 3 ij. 9Jj.)- Of 
twenty cases, in which statements on this point are made, 
death occurred in ten in from six to fifteen, and in five, in 
from one to three minutes. 

The pathological alterations which have been hitherto 
discovered, furnish, on account of their inconstancy and 
their general nature, no clear insight into the immediate 
causes of death. The investigation of the English Chloro- 
form Committee, which were made, as a rule, upon dogs, 
showed, like many analogous observations on man, a great 
distention of all the cardiac cavities with blood, in which 
respect those of the right side surpassed those of the left. 
In some cases, bubbles of gas were found in the veins of 
men who fell victims to chloroform, as v. Langenbeck, 
among others, had already stated in the year 1848. This 
fact induced some French investigators to regard death 
from chloroform as due to a development of chloroform 
vapor in the veins, or as a consequence of embolism of the 
pulmonary capillaries produced by this gas. The renewed 
observation of the collection of gas in the vessels has recently 
led to an experimental investigation of this phenomenon. 
v. Recklinghausen, in three cases in which respiration had 
continued for some time after the cessation of the pulse, 
and death had then occurred, found bubbles of gas in the 
larger venous trunks and the heart, although no traces of 
decomposition could be discovered on the bodies. Son- 



176 INCIDENTAL EFFECTS OF DRUGS. 

nenberg, 1 in his experiments upon animals, made in conse- 
quence of this observation, demonstrated the develop- 
ment in the vessels, of a gas which was found to be 
nitrogen, after the administration of chloroform, but failed 
to discover the exact conditions under which the process 
occurs. In his opinion, one may imagine either a mechani- 
cal separation of nitrogen, or its liberation, under peculiar 
conditions of pressure, inside the blood-vessels, in the pres- 
ence of chloroform. 

This demonstration of the liberation of a gas which 
takes place in the vessels after the inhalation of chloro- 
form is of great importance, from a general toxicological 
stand-point, but leads us no nearer to an explanation of the 
fact that in rare cases, in spite of the greatest care in the 
administration of chloroform and in watching the patient, 
death occurs ; while, on the other hand, when the same 
chloroform is used and much less care is taken, many other 
patients are anaesthetized without any unpleasant accident. 
Of course, a large number of conditions have, in the course 
of time, been advanced as the causes of badly-borne or fatal 
chloroform inhalations ; but we have thus far not been in a 
position to regard ajny one of them as the universal and 
exclusive etiological factor in such cases. Therefore so 
apodictical a statement as that made by Sedillot, 2 and, later 
also, by Yvonneau 3 : " Le chloroforme pur et bien employe 
ne tue jamais," cannot be accepted as proven, since there 
are probably other factors which may, under certain cir- 
cumstances, cause the fatal termination of an anaesthesia. 

All the conditions which have hitherto been held respon- 
sible for death from chloroform may be arranged in three 
groups. They comprise : 

1. The quality of the chloroform. 

1 Sonnenberg, Tageblatt der Naturforscher-Versammlung zu Baden-Baden, 
1879, p. 29. 

2 Sedillot, Gazette de Strassbourg, 1851, 7, 11. 

3 Yvonneau : De l'emploi du Chloroforme, Paris, 1853. 



NARCOTICS. 177 

2. The method of administration. 

3. The mental and bodily condition of the patient. 

1 . The bad quality of the chloroform is usually regarded as 
the most important of the causes which lead to the occur- 
rence of hurtful incidental effects, or death, from its use. It 
is well-known that chloroform may be adulterated in 
various ways, either designedly or accidentally. The 
former consist in the addition of alcohol or ether, and the 
latter are either the result of the method of manufacture 
of the drug, or are due to its spontaneous decomposition 
under the influence of diffuse sun-light. The impurities 
which occur during the process of manufacture consist, as 
a rule, of either a mixture of acetyl and its chlorine deriv- 
atives, or of fusel oil, and are recognized by the production 
of a black or red color on the addition of concentrated 
sulphuric acid to chloroform. The products of the spon- 
taneous decomposition of chloroform may be : free chlo- 
rine (shown by the appearance of a red color when chlo- 
roform is dropped into a dilute solution of iodide of 
potassium); hydrochloric acid (the chloroform becoming 
cloudy on the addition of nitrate of silver), and hypochlo-- 
rous acid (the test for which is the bleaching of a strip of. 
blue litmus-paper when dipped into chloroform). Higher 
chlorine compounds may also be found in chloroform, such 
as ethene chloride (Dutch liquid), ethyl chloride, tetra- 
chlorethene, ethidene chloride, trichlorethane, tetrachlore- 
thane, allyl chloride, amyl chloride, and amylene and 
aldehyde. 

All of these impurities of an organic nature, the major- 
ity of which may be qualitatively demonstrated, usually 
betray their presence by an alteration in the specific 
gravity and the boiling point of the chloroform. Officinal 
chloroform has a specific gravity of 1.596, absolutely pure 
chloroform at 15 C. (59 F.), a specific gravity of 1.502; 
at 17.5 C. (64 F.), of 1.497, and at 20 C. (68° F.), of 1.493. 



12 



178 INCIDENTAL EFFECTS OF DRUGS. 

The presence of one-half per cent of alcohol lowers its 
specific gravity to 1.493 at 15 C. (59 F.), of one per cent, 
to 1.485. Ether, ethene chloride, and amylene also lower 
the specific gravity, while tetrachlorethene, tetrachlor- 
ethane and trichlorethane raise it. The boiling point of 
officinal chloroform is always 61-62 C. (142 F.). It is 
lowered by ethylic chloride, ether, and amylene, and is 
raised by alcohol, ethylenic chloride, and the rest of the 
above-mentioned higher chlorine compounds. The Eng- 
lish chloroform and that prepared from chloral, both of 
which are said not to undergo spontaneous decomposition, 
have a specific gravity of less than 1.49. 

Nearly all the more highly chlorinated compounds 
which have been mentioned produce unpleasant incidental 
effects when inhaled, and are readily capable of causing 
bad accidents, particularly when certain predisposing 
bodily conditions are present. Although such adulterations 
have as yet been found in only a few of the recorded 
cases, it is evident that no careful investigation has been 
made in the majority of instances. Worthy of notice is an 
observation of Bartscher, 1 bearing upon the differences as 
regards their action upon man, between pure chloroform 
and that containing other chlorinated compounds. While 
he could very easily produce anaesthesia by using fresh 
chloroform, a preparation which had stood for several 
weeks caused a number of injurious effects, both during 
anaesthesia, as well as in the course of the succeeding 
twenty -four hours. That changes took place in the chlo- 
roform while standing, was shown by the fact that it at 
first lost its somewhat pleasant, sweetish taste, gradually 
acquired a burnt odor, and later produced disagreeable 
irritation in the nose and throat. In such cases, the 
presence of hydrochloric acid, alcohol, and ethene chlo- 
ride in the chloroform, could always be demonstrated. 

1 Bartscher, Berl. klin. Wochenschrift, 1866, p. 325. 



NARCOTICS. 



179 



The injurious incidental effects ceased when he began to 
administer rectified chloroform. Berghmann 1 found a 
small quantity of allyl chloride in a specimen of chloro- 
form which had caused death during complete anaesthesia. 
In another case reported by Hiiter 2 (death during com- 
plete anaesthesia), only one-third of the chloroform dis- 
tilled over at the proper temperature (62 C, I43f° F.). 
The remainder boiled only at 70-75 C. (158-167 F.) ; and 
even at 8o° C. (176 F.), a large residue remained. It 
contained neither hydrochloric acid nor free chlorine. It 
seemed to have been prepared from impure alcohol, and 
contained chlorinated products. In occurrences of this 
kind, one is compelled to regard the bad quality of the 
chloroform as an important factor in producing death, 
particularly when the patient was robust, and suffered 
from no pre-existing disease. In order to be secure 
against accidents of this kind, it is well to employ, accord- 
ing to the custom of Hiiter, only a chloroform the boiling 
point of which has been previously determined. 

2. An improper manner of administration, i. <?., the inhala- 
tion of chloroform insufficiently mixed with atmospheric 
air, is much more apt than pure chloroform to produce 
threatening phenomena or death. In England, particu- 
larly, the utmost weight is attached to this factor in the 
etiology of death from chloroform. Thus the English 
chloroform committee 3 expressed the opinion that those 
cases of death which occur before the beginning of anaes- 
thesia, as well as those in which a fatal result takes place 
from syncope previous to the beginning of the stage of 
excitement, are due to the sudden inhalation of too con- 
centrated vapors of chloroform. Holmgreen 4 has since 



1 Berghmann, Refer, in Kappeler, 1. c., p. 88. 

2 Huter, Berl. klin. Wochenschr., 1866, No. 30. 

3 Medico-Chirurg. Transact., xlvii., 1864, p. 323. 

4 Holmgreen, Virchow-Hirsch's Jahresbericht, 1867, i., p. 450. 



180 INCIDENTAL EFFECTS OF DRUGS. 

succeeded in proving, by experiment, that the slowing or 
arrest of the heart's action which appears after the inhala- 
tion of too concentrated vapors of chloroform, in the 
beginning of its administration, occurs in consequence of 
an influence reflected from the branches of the trigeminal 
in the nasal and pharyngeal mucous membranes upon the 
pneumogastric nerve. If these parts are protected from 
contact with the chloroform vapors, by causing them to be 
inhaled through a tracheal canula, these disturbances in 
the respiration and pulse fait to occur, as the chloroform 
committee found. Lallemand, Perrin, and Duroy 1 also 
witnessed the speedy occurrence of death in animals 
which inhaled the too concentrated vapors of chloroform. 
A mixture of four parts of chloroform with one hundred 
parts of air they found harmless, a mixture of eight parts 
to one hundred deadly. In order to avoid the dangers of 
too concentrated chloroform vapors, the chloroform com- 
mittee established as the normal standard for inhalation 
a mixture of three and one-half parts of chloroform with 
one hundred parts of air, and, as a maximum, four and a 
half parts of chloroform to one hundred of air. 

Apparatus for the preparation of this or similar mix- 
tures have been constructed by Clover and others. They 
are, however, too complicated, and do not furnish a more 
certain protection against the dangers of chloroform, 
which lie in the degree of concentration, than the ordi- 
nary chloroform-basket in the hands of a man familiar 
with its use. By a gradual administration, beginning 
with small quantities of chloroform, and a free admission 
of fresh air to the respiratory passages, the accidents 
which may result from too high a degree of concentration 
of the vapor may be avoided with absolute certainty. 
3. The mental and physical condition of the patient far 

1 Lallemand, Perrin, Duroy : Du role de l'alcool et des anesthesiques dans 
rorganisme, Paris, i860. 



NARCOTICS. l8l 

exceeds, in importance, both the factors already men- 
tioned, in the production of dangerous conditions during 
the administration of chloroform; but just as little as we 
are justified in regarding the bad quality of the chloroform 
or its faulty administration as the sole cause of all deaths 
from this agent, or even of its hurtful incidental effects, 
just so little is the view permissible that any one of the 
conditions still to be mentioned is the exclusive factor 
in the production of perverse effects of the drug. The 
following conditions pertaining to the mental and bodily 
spheres, have by different authors been held responsible 
for such occurrences : 

a. An idiosyncrasy against chloroform. 

Clemens, 1 Billroth, 2 and Denonvilliers 3 may be regarded 
as representatives of this view. The latter regards the 
death of those persons who die very suddenly after inhal- 
ing a few whiffs of chloroform, as due to an idiosyncrasy, 
and cites as analogues the specific action of other medicinal 
agents, such as iodide of potassium, etc., upon certain 
persons. Clemens states that he has often met with the 
chloroform idiosyncrasy, and that it is characterized by 
this peculiarity, that persons who submit to an operation 
with the earnest desire to pass through it without pain, 
with the aid of chloroform, spring up after the first few 
inhalations of the drug, and prefer to submit to the opera- 
tion without anaesthesia. Denonvilliers is of the opinion 
that the peculiar susceptibility to the toxic action of chlo- 
roform found in certain individuals is of only temporary 
duration, in view of the fact that patients who, a short 
time previously, have borne the first employment of the 
agent without unpleasant effects, may succumb to its 

1 Clemens, Archiv f. Heilkunde, 1824, p. 500. 

2 Billroth, Wiener medic. Wochenschrift, 1868, No. 47. 

3 Denonvilliers, Bulletin de l'Academie de Medec., Juin, Juillet, 1857, T. 
xxii. 



1 82 INCIDENTAL EFFECTS OF DRUGS. 

second administration. In the introduction to this work,, 
the attempt has already been made to furnish a substratum 
for the intrinsically meaningless conception of an "idio- 
syncrasy." If we understand by this term a certain bodily 
condition Avhich, being congenital, consists either in an 
abnormal condition of the structure and the arrangement 
of any of the systems of the body, or is temporarily devel- 
oped as a consequence of certain functional disturbances 
in individual organs, we can, in given cases, easily explain 
the deviations from the normal action of chloroform, e. g. r 
the ready occurrence of reflex arrest of the heart's action, 
or the appearance of exanthemata or vomiting. 

b. Psychical depression. 

According to the opinion of the English chloroform 
committee, persons who are under the influence of any 
emotion, such as fright, terror, care, etc., show a special 
disposition to succumb to the action of chloroform. The 
same is true of individuals who have received injuries 
from any suddenly exerted force, and present that group 
of symptoms known as "shock," consisting in mental 
apathy or unconsciousness, smallness of the pulse, pallor 
of the face, etc. 

c. Bodily weakness. 

It is a matter of indifference whether this condition was 
caused by prolonged sickness, excessive loss of blood, or 
venereal excesses. Paget 1 attributed the death of a girl 
who had led a very disorderly life, who was about to be 
brought under the influence of chloroform, in order to 
have a carcinoma of the vagina removed, and died after 
the first few inhalations, to her debilitated bodily condition, 
produced by her dissolute life. In order to elucidate this 
point, Clemens 2 made experiments upon dogs, rabbits, 
guinea-pigs, and large insects, which are said to have re~ 

1 Paget, Lancet, October, 1853. 

2 Clemens, 1. c, p. 504. 



NARCOTICS. 183 

suited in showing that after immoderate sexual indulgence, 
death from chloroform was much more quickly produced, 
and by much smaller doses, than in the case of healthy 
animals. 

d. Diseases of the heart, particularly fatty degeneration of 
the muscular tissue. 

Fatty degeneration of the heart, in spite of the negative 
results. in this regard obtained by Kidd, 1 in persons who 
died during anaesthesia by chloroform, must be regarded 
as one of the most important adjuvants in the causation of 
death from this agent. In fifty-six such cases, Sansom 2 found 
it. eighteen times, and in the list collected by Kappeler 3 it 
occurred sixteen times in sixty autopsies. In spite of this 
high percentage, Kappeler attributes only a relative, and 
not an absolute danger to fatty heart, because, on the one 
hand, among those who suffered from this affection, some 
had previously taken chloroform without accidents, and on 
the other, in amputations for senile gangrene, in which 
disease, as is well known, atrophy and fatty degeneration 
of the heart are common, he never saw any disquieting 
phenomena produced by the administration of the drug. 
This limitation of fatty degeneration of the heart to the 
position of an only relatively dangerous complication is 
entirely justifiable, because in view of the great frequency 
of its occurrence in a slight degree, investigation into the 
causes of death from chloroform in a given case may easily 
fall into wrong channels and lead to erroneous conclusions. 

e. Chronic alcoholism. 

It has not yet been explained why drunkards react in 
such an abnormal manner to the inhalation of chloroform, 
as is so often observed in operating-rooms. Such indi- 
viduals require not only much larger quantities of chloro- 

1 Kidd, British Medical Journal, 1862, January 25th, May 24th. 

2 Sansom: Chloroform, its action and administration. London, 1866. 

3 Kappeler, 1. c, p. T2i. 



1 84 INCIDENTAL EFFECTS OF DRUGS. 

form than healthy persons, in order to be fully anaesthetized, 
but they also manifest intense excitement, as shown by 
excessive muscular activity, screaming and struggling, and 
in the unconscious endeavor to leave the operating table. 
In the condition of relaxation which follows this stage of 
excitement, there often occurs a state of collapse, attended 
with stertorous respiration, which may easily lead to a 
fatal result. It is natural to regard a combined action of 
alcohol and chloroform as the cause of these phenomena, 
attempts to explain which have been made from different 
stand-points. Lefort is of the opinion that the organism 
weakened by alcohol is unable to bear the action of chlo- 
roform — an explanation which amounts to nothing more 
than a statement of the fact. According to Scheinesson, 1 
chloroform causes both a lessening of heat production and 
a retardation of the bio-chemical processes which take 
place in the organism. Alcohol produces the same effect, 
and the sum of their united actions ma)', in the case of 
drunkards, induce deleterious incidental effects or even 
fatal results. It is difficult to believe that such processes 
— lowering of temperature and diminution of the chemical 
processes of the body — can take place in so short a time as 
from the beginning of anaesthesia to the production of 
sleep, and exert so powerful an action. The opinion seems 
much more plausible, that the material changes produced 
in the central nervous system by chronic alcoholism mani- 
fest themselves, during the action of chloroform, by func- 
tional changes of a higher degree, and in a much more 
deleterious manner, than in the case of an ordinary de- 
bauch in alcoholic beverages. From this point of view all 
the abnormal symptoms would be regarded as either 
directly or indirectly of central origin. 

1 Scheinesson, Untersuchungen liber den Einfluss des Chloroforms auf die 
Warmeverhaltnisse der Organe und den Blutkreislauf. Dorpat, i863, und 
Archiv der Hei kunde, Bd. x., 1861. 



NARCOTICS. 185 

According to the data collected by different authors, the 
proportion of deaths from chloroform occurring in drunk- 
ards varies between ten and thirteen per cent. 

In the preceding pages we have discussed the causes 
which, singly or combined, may lead to death from chloro- 
form, and have also indicated the symptoms which attend 
it. It is fortunately comparatively rare, occurring about 
once in three thousand cases of the administration of the 
agent, and it is probable that this proportion would be 
rendered still smaller by a more careful investigation of 
the real causes of such accidents. The attainment of this 
result, a diminution of the death rate, would be also 
much facilitated by a careful attention to the trivial abnor- 
mal phenomena which occur in the majority of cases, and 
not infrequently, as has been already remarked in the be- 
ginning of this article, precede death from chloroform. 

Among these is the tonic spasm of the muscles of masti- 
cation, and the posterior muscles of the tongue, which 
frequently occurs during the stage of excitement. The 
tongue is spasmodically drawn backwards by the stylo- 
glossal and stylo-pharyngeal muscles, and therefore presses 
the epiglottis downwards. In this manner a mechanical 
closure of the entrance to the larynx is produced, and if 
this be not at once relieved, mechanical suffocation occurs, 
attended with lividity of the lips, exophthalmus, etc. 

Another disagreeable incidental effect is vomiting, which 
appears in all stages of anaesthesia. It nearly always 
appears when the stomach is full, and may become so ob- 
stinate as to last even twenty-four hours after completion 
of the anaesthesia. It is usually attended with thirst, head- 
ache, and depression of spirits. An entrance of the con- 
tents of the stomach into the air-passages occurs but 
rarely while it is present, as the patients usually wake up 
when it begins. In the one hundred cases of death col- 
lected by Kappeler, death from suffocation in this manner 
occurred only twice. 



1 86 INCIDENTAL EFFECTS OF DRUGS. 

In rare instances, icterus and the passage of the coloring- 
matter of the bile into the urine have been observed after 
the inhalation of chloroform. 

The greatest attention is, however, demanded by the 
phenomena pertaining to the organs of respiration and 
circulation. It has already been stated that reflex apncea 
may occur after the first few inhalations of chloroform. 
In this event there suddenly occurs, once or repeatedly, a 
pause in respiration, lasting a shorter or longer time, or 
the respiratory acts become constantly slower and more 
shallow, or inspiration fails entirely, after a long jerking 
expiration. These phenomena either disappear spontane- 
ously or are easily relieved by the aid of the physician. 
Irregularity or complete failure of the pulse, attended 
with pallor of the face, is also a common occurrence. These 
symptoms 'may also disappear spontaneously, in strong 
contrast with that group of phenomena known as chloro- 
form-syncope, in which the radial pulse suddenly disap- 
pears, the heart-sounds become almost inaudible, the 
respiration ceases, and the face becomes like that of a 
dying man. Restoration to a normal condition is possible 
in very few such cases. 

Another incidental effect of chloroform, interesting only 
from a pathognostic standpoint, was observed by Richet. 1 
During a normal anaesthesia, there appeared dark-red 
spots, spread over the whole bod) 7 , which presented the 
appearance of a purpura hemorrhagica, but disappeared 
under pressure. 

Of almost equal interest with these incidental effects 
produced by the inhalation of chloroform, are those ex- 
cited by the application of this agent to the healthy skin 
or mucous membranes. Redness and a feeling of pain are 
produced by rubbing chloroform upon the normal skin, 
and not infrequently there appears an urticaria-like or an 

1 Richet, Journal de la Socie'te des Sciences medic, de Bruxedes, 1851. 



NARCOTICS. 187 

eczematous eruption. Vesiculation may occur if the ap- 
plication be continued. When chloroform is applied to 
certain very sensitive portions of the skin, e.g., the scro- 
tum, the pain which it causes is so intense and persistent 
that patients generally refuse to allow a renewed employ- 
ment of the agent. For this reason it is not advisable to 
follow the method of treating orchitis recommended by 
Bouisson,' enveloping the scrotum in compresses saturated 
with chloroform. 

Upon wounds and mucous membranes, chloroform pro- 
duces pain of a relatively much more intense degree. When 
it falls upon the lips during anaesthesia, fissures sometimes 
form upon the affected parts, or the mucous membrane is 
thrown off in flakes. 

Treatment of Accidents from the Use of Chloroform. 

The disturbances in the respiration and pulse demand 
energetic interference more than all others. Mechanical 
closure of the rima glottidis by the spontaneous falling 
back of the tongue, or in consequence of the spasmodic 
traction exerted by the posterior lingual muscles, is 
relieved by forcing open the mouth, by Heister's speculum, 
if necessary, and by drawing the tongue forcibly for- 
wards by the tongue-forceps or a loop of thread, and 
cleansing the mouth from mucus. In many cases, the 
same end is accomplished by the more simple manipula- 
tion of lifting the lower jaw, as described by Heiberg. 2 
The operator stands behind the reclining patient, places 
the thumbs on the symphysis of the lower jaw, presses the 
second joints of the flexed index fingers behind the poste- 
rior borders of the ascending ramus of the jaw, thus hold- 
ing the entire bone firmly between his hands, and draws it 
forcibly forwards. In order to accomplish the same 

1 Bouisson, Annales des maladies de la peau, Janvier, 185 1. 

2 Heiberg, Berliner klin. Wochenschr., 1874, P 449- 



1 88 INCIDENTAL EFFECTS OF DRUGS. 

object, Kappeler stands before the patient, places his 
thumbs close to the nose of the patient, upon the anterior 
wall of the upper jaw, and with the two distal phalanges of 
his bent index fingers, placed behind the angles of the 
lower jaw, draws the bone forwards. In this manoeuvre, 
the tongue and the hyoid bone are also drawn forwards, 
and the epiglottis, which follows them, is placed upright. 

If, in spite of the fact that air has free access to the 
lungs, there occur disturbances of respiration and circula- 
tion, simultaneously with a change in the color of the 
patient's face, the use of chloroform should be immediately 
stopped, an abundance of fresh air provided for, and, if 
the anaesthesia be still incomplete, as shown by the fact 
that the organism still responds by reflex movements to 
external irritation, recourse should be had to cold douches 
and injections of cold w T ater into the nasal cavities, and the 
patient should be made to inhale strongly-smelling sub- 
stances, such as ammonia or its carbonate. Billroth x is, 
however, perfectly right in insisting that no time should 
be wasted with such measures in complete anaesthesia, 
in which they can be of no possible use, but the operator 
should at once resort to artificial respiration. 

A number of methods have been recommended for this 
purpose, such as : 

i. Inflation of the lungs from mouth to mouth, Avhile 
expiration is aided by compressing the lower part of the 
thorax, and the nostrils are kept completely closed. In 
using this method, as Billroth observed, a portion of the 
air goes into the stomach. 

2. Inflation by means of bellows. Plouviez 2 introduced 
the nozzle of a bellows into one nasal opening or into the 
throat, and suddenly forced a stream of air into the lungs. 



1 Billroth, Wiener medic. Wochenschrift, 1868, p. 795. 

9 Plouviez, Journal de la Soc. des Sciences medic, de Bruxelles, 1857, p. 14. 



NARCOTICS. !8q 

The breast and abdomen of the patient were at the same 
time alternately compressed. 

3. Inflation by means of a laryngeal catheter. If it be 
impossible to introduce a catheter into the larynx, on 
account of spasm of the posterior lingual and upper pha- 
ryngeal muscles, tracheotomy must be performed, and air 
introduced through the tracheal canula by the mouth 
or bellows. 

4. The method of Marshall Hall, in which the patient, 
several times in each minute, is laid first upon the back 
and then upon the side, at regular intervals, pressure 
being exerted upon the back every time the body is 
turned over. 

5. Galvanization of the phrenic nerve. The positive 
moistened electrode of a constant battery or a sliding in- 
duction apparatus is placed upon the phrenic nerve in the 
neck, over the scaleni muscles, and the negative over the , 
precordium, under the edge of the ribs, or both poles are 
placed on the sides of the neck, at the outer edges of the 
sterno-cleido-mastoid muscles. 

6. Allowing the patient's head to hang down, as recom- 
mended by N61aton, or suspending the body by the feet, 
the proceeding adopted by Spoerer 1 in one case with 
success. 

7. Acupuncture or electropuncture of the heart. This 
was attempted by Hiiter 2 in a case of arrest of the heart's 
action, as a last resort, but without success. He intro- 
duced a needle two inches long at the left edge of the 
sternum, into the fourth intercostal space, to a depth 
of three-quarters of an inch, and a second at a point 
nearer the nipple, and somewhat lower down. 

The occurrence of one or more attacks of vomiting dur- 
ing anaesthesia, or on awaking from it, rarely requires the- 

1 Spoerer, Petersburger medic. Zeitschrift, 1866, p. no. 

2 Hiiter, Berliner klin. Wochenschr., 1865, p. 486. 



: 9 o 



INCIDENTAL EFFECTS OF DRUGS. 



rapeutic interference. If it become more frequent, pieces 
of ice, or champagne should be administered. The appli- 
cation of cold compresses to the epigastrium usually 
succeeds in arresting it. 

IODOFORMUM. 

» 

After the administration of iodoform, aside from the 
odor which attends its elimination, only such incidental 
effects have been hitherto observed as are due to a cen- 
tral action of the agent. After Italian authors had called 
attention to the ansesthetic or hypnotic effects of this drug, 
Binz x showed that this action was due to a liberation 
of iodine in the body. " Since a yeast-cell, when touched 
by iodine, decomposes no more sugar, and a colorless 
blood-cell sends out no more processes, a brain-cell, under 
the same influence, suspends its peculiar activity ; it no 
longer receives impressions from without, and ceases 
to produce impulses for its centrifugal filaments. It 
sleeps, if the condition produced by iodine be reparable ; 
it dies, if its structure has been organically altered." 

Proof of the correctness of this deduction is furnished 
by a few cases communicated by Oberlaender, 2 among 
others, in which incidental effects of central origin were 
produced by the use of iodoform. A female patient, 
affected with gummy tumors, took forty-two grams 
( 3 xss.) of iodoform in the form of pills, during a period of 
eighty days. At the expiration of this time, she was 
attacked by dizziness, a feeling of weakness, and diplopia. 
These symptoms lasted two days and a half. In spite of 
the discontinuance of the remedy, she began to vomit and 
fell into a deep sleep, from which she could be aroused 

1 Binz, Archiv f. experiment. Pathologie u. Pharmakologie, Bd. viii., p. 310 
u. Bd. xiii., p. 159. 

' 2 Deutsche Zeitschrift fur pr. Medicin, 1878, No. 37. Ref. in Archiv fur 
Dermatologie und Syphilis, 1879, p. 372. 



NARCOTICS. igi 

with great difficulty. For several days this drowsiness 
alternated with conditions of excitement, foolish talking, a 
feeling of great anxiety, and twitchings of the muscles of 
the face and trunk. Not before the twelfth day after the 
beginning of these symptoms was she able to stand alone 
and walk a short distance. 

The second case was that of a person affected with 
ulcers of the throat, who had taken five grams (gr. lxxv.) 
of iodoform in pills, in seven days. Somnolence ap- 
peared, the gait became clumsy and uncertain, and the 
patient complained of headache over the whole circum- 
ference of the head. After these symptoms had lasted for 
one day, she fell into a comatose condition, which lasted 
five davs, during which time, however, she reacted 
promptly to external irritation, making warding-off ges- 
tures. Articles of food were swallowed. The urine gave 
a distinct iodine reaction. Not until fourteen days after 
the appearance of the first symptoms of disease could the 
patient be regarded as cured. 

The probability of confounding such conditions with 
cerebral syphilis is not great, because in £he latter no im- 
provement is obtained by expectant treatment. 

Methyleni Bichloridum. 

The bichloride of methylene, or chloromethyl, has been 
much employed since the year 1867, when Richardson 
first recommended it as an anaesthetic. It was said to be 
preferable to chloroform on account of being less dan- 
gerous, and producing only insignificant incidental effects, 
or none at all. But it has been since discovered that 
this substance has no particular advantages over chloro- 
form, and is hardly less dangerous. Hollander, 1 who used 
it during the extraction of a tooth, was compelled in 
one case to administer nearly thirty grams ( 3 i.) in 

1 Hollander, Berliner klin. Wochenschrift, 1867, p. 49. 



IQ2 INCIDENTAL EFFECTS OF DRUGS. 

order to produce anaesthesia, and afterwards noticed 
a condition of excitement, violent vomiting, and a feel- 
ing of fulness of the head, which lasted nearly an hour 
after the patient had regained consciousness. Hegar 
and Kaltenbach 1 witnessed the occurrence of attacks 
of asphyxia after the inhalation of the bichloride of me- 
thylene, and found excoriations on the lips and cheeks, 
when it was administered by the ordinary wire basket, 
instead of Junker's apparatus. 

In addition to these trivial accidents, fatal results have 
also been known to occur after the use of this agent. 
They took place either suddenly without respiratory dis- 
turbances or change in the color of the face, or the res- 
piration became gasping, the radial pulse small and 
fluttering, the color of the face pale or livid, and death 
followed, with absolute cessation of the pulse, but without 
convulsions. 

^Ethylideni Chloridum. 

Ethylidene chloride, which has been recommended as 
an anaesthetic, 8 and occasionally successfully employed for 
this purpose, a fluid which boils at 6o° C. (140 F.), produces 
a speedy and quiet anaesthesia, with equable action of 
pulse and respiration. Nevertheless, the further employ- 
ment of the agent has been arrested by the occurrence of 
a death during anaesthesia produced by it. 

.Ether Sulphuricus. 

Like chloroform, ether produces during its inhalation a 
number of accidents which are either of a transitory nature 
or lead to fatal results. Among the former is an obstinate 
vomiting which may continue not only during anaesthesia, 
but also after the operation, and paroxysms of coughing. 

1 Hegar u. Kaltenbach: Operative Gynakologie, 1874, p. 25. 

2 O. Liebreich, Berliner klin. Wochenschr., 1870, No. 31. 



NARQOTICS. I9 3 

The latter is probably due to the fact that, in consequence 
of the free secretion from the salivary glands which always 
takes place during etherization, saliva flows into the air- 
passages. 

The dangerous symptoms are those which pertain to 
the respiration and circulation. Paleness or cyanosis of 
the face appear, the respiration at the same time becomes 
irregular or ceases entirely, and the pulse becomes 
small and finally imperceptible. Cases have been pub- 
lished in which, although the patients had reached this 
dangerous state, restoration was successfully accomplished 
by the aid of artificial respiration, drawing the tongue 
forwards, etc. If, however, the whole mechanical thera- 
peutical apparatus is not at once employed against these 
disturbances, death occurs suddenly, either with simul- 
taneous cessation of the respiration and pulse, or persist- 
ence of the latter for a few minutes longer than the former. 
In the majority of the cases reported by English authors, 
death occurred without premonitory symptoms. In some 
there appeared violent muscular excitement, cyanosis or 
turgescence of the face, dilatation of the pupils, or labored 
breathing. 

The measures to be employed for the relief of such phe- 
nomena are the same as those recommended in syncope 
from chloroform. In order to prevent them, the head of 
the patient must be elevated so as to obviate the entrance 
of saliva into the air-passages. Attention must also be 
paid to the degree of concentration of the ether-vapors, 
and the purity of the preparation used, as in the case of 
chloroform. 

The habitual use of ether, as Ewald 1 observed in the case 
of a so-called "ether-breather," causes general weakness, 
muscular tremors, and a peculiar annoying odor of the 
body. 

1 Ewald, Berliner klin. Wochenschrift, 1875, p. 133. 
13 



!Q 4 INCIDENTAL EFFECTS OF DRUGS. 



Amyli Nitritum. 

The nitrite of amyl, a product of the action of nitric 
acid upon amylic alcohol, was regarded, during the early 
years of its employment, provided that it contained no 
noxious ingredients, such as hydrocyanic and nitric acids, 
as a harmless substance which produced no disquieting 
phenomena. Incidental effects upon the functions of 
various organs have, however, since been frequently 
observed after the use of this agent. Their appearance is 
dependent upon the individuality of the patient, but they 
occasionally occur also in persons who are accustomed to 
the inhalation of the drug. 

Among the organs of special sense, the eye is most fre- 
quently affected in this respect. The subjective color- 
sensations which occur are not alike in all cases, as 
Schroter 1 found in a number of patients, but are only now 
and then very distinct in many cases, and are not identical 
at every inhalation. In their typical form they consist, 
according to Pick, 2 in the appearance of an intensely yel- 
low halo around any fixed point upon a clear background. 
This yellow circle is surrounded by a bluish-violet border. 
This phenomena is probably nothing more than the pro- 
jection of the macula lutea, and the bluish-violet border its 
complementary color. The patients treated with nitrite of 
amyl by Sander 3 stated of their own accord, after the in- 
halation, that for some time everything had seemed yellow 
to them. It could not be clearly determined whether or 
not this phenomenon was due to the yellow color of that 
portion of the field of vision which corresponds to the 

1 Schroter, Zeitschrift f. Psychiatrie, Bd. 32, 5, p. 527. 

2 Pick, Centralblatt f. d. medic. Wissenschaften, 1873, p. 866. 

3 Sander, Medicin.-psycholog. Gesellsch. zu Berlin. Sitzungvom 4. December, 
1874. 



NARCOTICS. 

macula lutea. The yellow vision disappears only after 
some minutes, growing gradually paler. 

Schroter also noticed a diminution of the clearness of 
sight. Patients who had inhaled nitrite of amyl for a cer- 
tain time were unable, e.g., to see clearly the figures on a 
large clock, which seemed blurred to them. Normal 
vision returned immediately after they stopped using the 
drug. 

An abnormal action upon the central nervous system is 
but seldom observed. Veyrieres, 1 after a prolonged inha- 
lation, noticed in his own case giddiness and stupor lasting 
from six to eight minutes, followed by a headache lasting 
two hours. In some cases of disease of the brain, Schro- 
ter witnessed, during the inhalation of the drug, the ap- 
pearance, increase, or re-appearance of delirium of the 
senses. Bourneville 2 has reported similar observations 
After the use of nitrite of amyl this author noticed violent 
headache, a feeling of dizziness, and in hysterical cases, 
visual illusions, accompanying the yellow sight produced 
by the agent. 

After the inhalation of the drug, and to a certain extent 
as an after-effect, Sander observed profound collapse, 
which appeared suddenly and was characterized by faint- 
ing, falling to the floor, pallor of the face, smallness of the 
pulse, and cold clammy perspiration. Samelsohn 3 describes 
a similar case, in which a patient, while fully under the in- 
fluence of nitrite of amyl, made a few deep, spasmodic 
inspirations, and presented coldness of the skin, which was 
bathed in sweat, and a small, thready, and extremely slow 
pulse, while consciousness, although weakened, was not 
entirely lost. Urbantschitsch 4 has also called attention to 

1 Veyrieres, Virchow-Hirsch's Jahresbericht, 1875, i., p. 481. 
? Bourneville, Gazette medicale de Paris, 1876, No. 13. 

3 Samelsohn, Berliner klin. Wochenschrift, 1875, p. 349. 

4 Urbantschitsch, Wiener medic. Presse, 1877, 8. u. ff. 



!^6 ' INCIDENTAL EFFECTS OF DRUGS. 

the occurrence, in some cases, after the inhalation of even 
two drops of nitrite of amyl, of collapse, with paresis, or 
intense dizziness with difficulty of respiration. 

With regard to other incidental effects, the statement of 
Bourneville is of interest, that tremor of the lips and diffi- 
culty of mastication often follow the inhalation of nitrite 
of amyl. Urbantschitsch noticed dryness of the mouth 
lasting from twelve to twenty-four hours after its use. In 
some cases, instead of redness of the face, the first effects 
of its action are palpitation of the heart, a sense of oppres_ 
sion in the head and ears, and tickling in the throat. The 
last symptom was observed by Veyrieres also, while La- 
dendorf 1 noticed the occurrence of a violent dry spasmo- 
dic cough in a patient, on two occasions, during a four 
weeks' course of nitrite of amyl. A number of authors 
have also reported the occurrence of distressing nausea 
and vomiting after repeated inhalations of the agent. 

In using nitrite of amyl, care must be taken that it does 
not present an acid reaction. After standing for a long 
time, decomposition takes place even in a previously neutral 
preparation, leading to the formation of free nitric acid. 
This change may be prevented by adding a few small 
pieces of burnt chloride of calcium, or a little magnesia to 
the preparation. The presence of hydrocyanic acid is 
readily demonstrated by shaking the nitrite of amyl with 
water, and testing the latter for this substance. 

EVACUANTS. 

I.— PURGATIVES. 
Oleum Ricini. 

Some persons have an invincible repugnance to castor-oiI r 
and often suffer from nausea and vomiting when they take 

1 Ladendorf, Berliner klin. Wochenschrift, 1874, p. 539* 



EVACUANTS. I97 

it. The latter also occurs if the oil is no longer fresh, and 
free fatty acids have formed in it. In order to disguise the 
unpleasant fatty taste of the oil and render it more palata- 
ble, numerous vehicles have been recommended, such as 
wine, brandy, milk, and coffee. Starke 1 advised for this 
purpose the conversion of the oil into a soft paste, by add- 
ing to it sugar (1 : 3) or compound liquorice powder (1 : 2) 
and to afterwards add to this, cinnamon powder or some 
other corrective. 

Aloe. 

Accompanying the special action of aloes (the produc- 
tion of pasty, not watery stools, with moderate griping), 
in addition to a sensation of warmth and oppression in the 
epigastrium, and frequent eructation, there not infrequently 
appear congestive conditions of other abdominal organs, 
such as the kidneys and uterus. Pre-existing hemorrhages, 
particularly from the latter organ, may be increased to a 
dangerous degree by the action of this drug. After large 
doses of aloes in substance or the extract, abortive effects 
are also said to have been observed. Under such circum- 
stances the patients complain of pain in the region of the 
kidneys and uterus, and of a feeling of weight in the pelvis. 

If preparations of aloes are used for a long time, there 
occurs, in consequence of the persistent congestion of the 
descending colon and rectum, dilatation of the hemor- 
rhoidal veins, which may, in time, develop into true hem- 
orrhoids. Whether this occurs to the extent described 
by Fallopius, 3 who says that, of one hundred persons who 
constantly use aloes as a purgative, ninety suffer from 
hemorrhoids, is, however, doubtful, in view of the numer- 
ous other unrecognizable conditions which contribute to 
the production of this affection. A certain predisposition 

1 Starke, Berliner klin. Wochenscrift, 1879, p. 232. 

2 Fallopius: Opera omnia. De medicam. purg. simpl., Francoforti, 1600. 



igS INCIDENTAL EFFECTS OF DRUGS. 

to the occurrence of the above-described effects is shown 
by aged and delicate young persons. 

Fructus Colocynthidis. 

Colocynth belongs to the class of drastic purgatives, 
which probably exercise their peculiar action by virtue of 
a direct irritation of the intestinal mucous membrane. 
For this reason, the stools are not infrequently attended 
with violent tearing pain and tenesmus, and may even be 
bloody, especially .when the digestive tract is already in 
an irritated condition. 

TUBERA JALAP.E. 

Like most of the other resins and substances which con. 
tain resins, which receive their cathartic properties by 
virtue of a direct action upon the intestinal canal, jalap 
root, which is active only in the presence of bile or bile- 
salts, usually excites pain and rumbling in the abdomen. 
Nausea sometimes occurs as the expression of gastric 
irritation. Vomiting may also take place. Large doses 
frequently repeated may excite catarrhal inflammation of 
the gastro-intestinal mucous membrane. 

Gambogia. 

While small doses of gamboge, as a rule, produce no 
particular incidental effects, there appear, in some per- 
sons, even after o.i-c.2 gram (gr. iss.-iij.), pain in the 
abdomen, vomiting, and a decided increase in the quantity 
of urine excreted. 

HERBA GRATIOL/E. 

Gratiola, which was formerly much used as a cathartic, 
produces, as we learn from the numerous old publications 
concerning it, even in doses of 0.5-1 gram (gr. viiss.-xv.), 
in powder or decoction, not a cathartic effect, but nausea 



EVACUANTS. 1 99 

and vomiting, or, besides these symptoms, salivation, 
burning in the urinary passages, loss of appetite, and 
attacks of nymphomania, as Bouvier 1 noticed, when the 
drug was used in women per enema. It is probable that 
the age of the drug and its richness in gratiolin, the active 
principle of gratiola, is influential in determining the oc- 
currence of these symptoms. 

Flores Sulphuris. 

Sulphur, which has been much prescribed in a variety 
of chemical forms as a purgative, in the treatment of thora- 
cic affections and chronic metallic poisoning, may easily 
produce irritation of the stomach and intestines, with 
digestive disturbances, particularly when the canal is 
already in an abnormal condition. It is partially trans- 
formed by the alkali of the intestinal juice into an alkaline 
sulphate, and, as this is decomposed by the carbonic acid 
of the blood and tissues, with the formation of absorbable 
sulphuretted hydrogen, the skin and the expired air both 
smell of this gas. According to Wibmer, 2 this agent 
in large doses may produce a miliary eruption. 

When sulphur ointments are used, an artificial eczema 
is produced in some persons, which soon disappears after 
the use of the agent is stopped. 

Oleum Tiglii. 

In addition to its drastic cathartic action, croton oil, 
taken internally, frequently produces, in certain persons, 
an itching, burning taste in the mouth, warmth and dry- 
ness of the throat, eructation, nausea, and colicky pains in 
different parts of the abdomen. 

When applied to the skin as a derivative, there appears, 

1 Bouvier, Gazette de Sante. Aout, 18 16. 

2 Wibmer: Wirkungen der Arzneimittel, v., p. 276. 



200 INCIDENTAL EFFECTS OF DRUGS. 

after one or two applications, attended with itching and 
burning and slight fever, an erythema, and upon this 
there soon show themselves firm vesicles, with serous con- 
tents, sometimes discrete and sometimes running together. 
The contents become purulent one or two days after the 
vesicles burst, or there appear at once a large number 
of pustules, which form crusts within twenty-four hours. 
Secondarily, there appear not infrequently, especially on 
the scrotum, as Wibmer 1 states, herpetic eruptions, which, 
perhaps, owe their origin to an accidental transplantation 
of the drug, but may also be regarded as a true absorp- 
tive affection. The former seems the more probable view, 
because such eruptions are never observed after the inter- 
nal administration of croton oil. Tartar emetic, after the 
external application of which similar secondary eruptions 
are observed on the genital organs, produces eruptions 
when taken internally also, in which respect it differs 
from croton oil. 

According to M. Langenbeck, 2 the endermatic employ- 
ment of croton oil causes phlegmonous inflammation and 
suppuration. 

The retrocession of the above-described skin affections 
takes place in from three to eight days after stopping the 
drug, and is attended with moderate desquamation. Only 
a pale yellow color of the affected portions of skin remains 
behind. 



II.— EMETICS. 

Antimonii et Potassii Tartras. 

It is well known that tartar emetic, when applied to the 
skin, in solution or in the form of an ointment, produces 

1 Wibmer, 1. c, i.. p.. 215. 

2 M. Langenbeck : Die Impfung der Arzneikorper. Hannover, 1856, p. 84. 



EVACUANTS. 201 

both eczema (papules, vesicles, oedema) around the 
mouths of the glands, as well as extensive pustular dis- 
eases of this organ (ecthyma antimoniale). The deriv- 
ative method of treatment, in which this external appli- 
cation of antimony is still occasionally resorted to, causes 
intense pain to the patient. It is desired, as a rule, to 
produce only a slight inflammatory irritation, but instead 
of this, extensive tissue disturbances sometimes occur. 
Particularly during the application of the so-called " pox- 
salve " to the head, in the treatment of certain cerebral 
affections, such as dementia paralytica, there readily occur 
deep, crater-like, more or less complete losses of tissue, 
and sometimes even exfoliation of bone at the bottom 
of the lesion. Among the older reports upon this subject, 
mention should be made of that of Jacobi, 1 who, in the 
year 1819, saw in Wiirzburg several patients in whom, 
after the application of antimonial ointment to the entire 
scalp, both tables of the parietal bones were perforated, in 
consequence of a necrosis which resulted from the treat- 
ment. In view of such an occurrence, it is certainly not 
out of place to call attention to the fact, that Hebra long 
ago spoke in condemnation of such a " useless, injurious, 
and sometimes even dangerous proceeding." 

The internal use of tartarized antimony as an emetic, 
either alone or in combination with ipecac root, as well as 
the use of other preparations of antimony, is sometimes 
followed, especially in children, by conditions resembling 
collapse, on account of the very great power of the drug 
to produce slowing and weakening of the action of the 
heart. For this reason it is advisable to administer ana- 
leptics, such as wine, coffee, etc., immediately after each 
attack of vomiting. To the same cause are to be attri- 
buted all those dangerous symptoms and even fatal results 

1 Jacobi, Damerow's Zeitschrift f. Psychiatrie, Bd. xi., p. 369. Ref. in Schu- 
chard, Arzneimittellehre. Braunschweig, 1858, p. 226. 



202 INCIDENTAL EFFECTS OF DRUGS. 

which have been reported as occurring- during the shorter 
or longer administration of antimony, even in small doses 
and in adult cases. It is probable that in such cases the 
individuality of the patient plays an important role. 
Thus, Falot 1 reports three cases in which, after from one 
to three small doses of antimony, there occurred, in addi- 
tion to vomiting, delirium, and spasms, so great a prostra- 
tion of strength, that life could be saved only by the 
energetic use of stimulants. Similar observations were 
made by Beau, 2 who reported two cases of death from 
small doses of antimony. In these also, the symptoms 
were from the first those of the most pronounced weakness 
of the heart, very small pulse, general cyanosis, and strik- 
ing paleness of the face. Death took place, with increase 
of the prostration and coldness of the extremities. Al- 
though antimony is no longer employed so extensively as 
formerly, it is nevertheless still used as an emetic and ex- 
pectorant often enough to justify this reference to the 
possibility of an injurious action. 

Its employment in those who are the subjects of any 
pathological changes in the intestinal canal, no matter how 
insignificant they may be, such as catarrh, etc., should be 
carefully avoided, because, both after its external and 
internal use in such cases, inflammatory irritation and 
even deeper lesions of the gastric and intestinal mucous 
membranes are always produced. After its external ap- 
plication, this irritation occurs in consequence of an elim- 
ination of the metal into the stomach and intestines, as 
has been demonstrated by Radziejewski. 3 This inflam- 
matory irritation is probably also the cause of the vomit- 
ing, which is the result of a reflex action set up by irrita- 
tion of the central apparatus which presides over the 

1 Falot, Union medicale, 1852, p. 245. 

' 2 Beau, Bulletin de Therapeutique, September, 1856. 

3 Radziejewski, Archiv f. Anatomie u. Physiologie, 1871, p. 472. 



EVACUANTS. 203 

movements of vomiting-. Hyperemesis sometimes takes 
place. 

The caustic action of tartar emetic, as well as other pre- 
parations of antimony, e. g., Kermes mineral, also some- 
times finds expression during the internal employment of 
medicinal doses, in the formation of pustules and vesicles 
in the mouth, throat, oesophagus, and even in the larynx. 
Laennec 1 regarded these symptoms as secondary, pro- 
duced by a saturation of the body with the drug. Falck, 2 
on the other hand, insisted upon the purely local origin of 
such affections from the action of the tartarized antimony 
introduced into the body in a fluid form, because they did 
not occur when it was taken in the form of pills. Al- 
though we cannot accept the theory of a saturation of the 
body with tartar emetic, we must admit the possibility of 
the occurrence of the changes above mentioned in conse- 
quence of the action of the antimony which circulates in 
the blood ; because, after the administration of the agent, 
affections have been seen'of the skin, and of mucous mem- 
branes which primarily never came in contact with it. 
Thus, it has been proven by numerous observations that 
not infrequently, after the external use of antimony, pustu- 
lar eruptions develop secondarily, particularly on the gen- 
itals and inner surfaces of the thighs, even several weeks 
after inunction, without there having occurred a trans- 
portation of the drug by the fingers from the original 
point of application. Many cases have also been recorded 
in which, after the internal administration of tartarized 
antimony, pustular eruptions have appeared, by preference 
on the above-mentioned parts of the body, but also on 
others. Thus, Imbert-Gourbeyre 3 reports an observation 
of Gohlius, 4 in which, after a large dose of antimony, a 

1 Laennec, Gazette des Hopitaux, 1853, No. 6 

2 Falck, Canstatt's Jahresbericht liber die gesammte Medicin, 1853, v., p. 148. 

3 Imbert-Gourbeyre, Gazette medica'e de Paris, 1861, pp. 3, 17, u. ff. 

4 Gohlius: Medicin. practic, clinic, et forensis. Lipsise, 1735. 



204 INCIDENTAL EFFECTS OF DRUGS. 

red eruption appeared over the whole body. Boeck ' also 
saw a similar phenomenon, after the administration of 06 
gram (gnix^ of tartar emetic in the course of thirtv-six 
hours. Helbert' reports a similar experience. Two'pos- 
sibiht.es present themselves, as Hermann states, for the 
explanation of this phenomenon. As its cause we must 
regard either an irritative action upon peripheral nerves, 
leading to reflex inflammatory changes in the blood-ves- 
sels, or a direct action upon the vessels themselves. In 
this manner -engorgement of the capillaries of the skin, ex- 
udation, and later, the formation of pustules, would be 
brought about It is, however, possible, that the glandular 
organs of the skm may be thrown into an inflammatorv 
condition by the direct action of the drug 

The less severe forms of the antimonial eruption require 
no therapeutic interference. Extensive ulcerations should 
be treated according to ordinary surgical principles. The 
gastric symptoms require treatment, especially when a 
sense of weight and pain are felt in the epigastrium, and 
if only a short time have elapsed between the administra- 
tion of the antimony and the appearance of these symp- 
toms. For this purpose the stomach may be washed out 
opiates or other narcotic substances being added to the 
Huia used. If hypcremesis be present, vegetable astrin- 
gents, tannin, decoction of cinchona, etc., should be admin- 
istered, because in such a case there is probably some 
antimony in the stomach, and it would form insoluble 
combinations with these agents. 

Radix Ipecacuanha. 
Ipecac, which is now but seldom employed as an irri- 
tant to the skin, produces, as Bazin 8 found, when applied 

1 Boeck, Preussische Vereinszeitung, 1843, No. 8. 
* Helbert: De exanthema!, arte factis. GOttingen, 1844. 
Bazm: Lecons sur les affections cntanees artificielles. Paris, 1862, p. IG 6. 



EVACUANTS. 



205 



as an ointment (one part to two of lard), after two or three 
inunctions, a papular eruption, without disturbance of the 
underlying corium. Diffuse redness, with burning, first 
appears, and upon this small elevations are formed. These 
increase in size and number, and are attended with intense 
itching, while the skin between them may regain its nor- 
mal aspect. They finally become quite large, and of an 
intense red color, showing no tendency to run together, 
and disappear under pressure. After stopping the inunc- 
tion, the eruption takes a certain time, one or two weeks, 
to pass away. It finally disappears without desquamation 
or cicatrization. The itching persists until the eruption is 
entirety well. According to Delioux, 1 an ointment of 
ipecac, like tartar emetic, may produce umbilicated pus- 
tules, which, however, differ from those produced by the 
latter agent by healing without the formation of cicatrices. 

The repeated internal administration of small doses of 
ipecac may, through the local action of the drug, excite 
gastric and intestinal catarrh, and as a consequence, loss of 
appetite and diarrhoea. The latter usually takes place in 
those cases in which the drug fails to excite vomiting. 
The stools are then less copious, being usually slimy, or 
bilious and slimy, and are often tinged with blood. Ac- 
cording to Arnold, 2 ipecac not infrequently shows great 
differences in its action. Emesis is sometimes excited by 
0.6 gram (gr. ix.), while in other cases 2.4 grams (gr. 
xxxvi.) produce no such effect. The cause of this differ- 
ence lies partly in the individuality of the patient, and 
partly in the quality, origin, and age of the root. 

Emetin, the alkaloid of ipecacuanha, is more constant in 
its. action, but is also not free from the disadvantage of 
producing incidental effects. 

1 Delioux, Gazette de Paris, 1852, No. 6 u. ff. 

2 Arnold: Das Erbrechen und die Wirkung der Brechmittel. Stuttgart, 1840. 



2o6 • INCIDENTAL EFFECTS OF DRUGS. 

III.— DIURETICS. 

BULBUS SCILL^E. 

Squill and its active principle, scillitin, in addition to 
their diuretic action, sometimes produce nausea when 
given in small medicinal doses, and if such small quantities 
are taken for a long time, as in dropsical conditions, vomit- 
ing and watery diarrhoea with griping may occur. As its 
diuretic action becomes exhausted after a time, the drug 
is then usually ordered in larger doses. When this is 
done, the above-described symptoms may take place with 
greater intensity, and the patients may suffer from tickling 
and burning in the throat, attacks of colic, pain on mictu- 
rition and even hsematuria. These symptoms are the 
expression of a local irritant action of the agent upon the 
mucous membranes with which it comes into direct con- 
tact. The diminution in the frequency of the pulse, which 
is also often observed, is to be regarded as the result of an 
influence reflected from the stomach. 

Radix SarsaparilltF. 

Gastric disturbances, such as nausea, inclination to vomit, 
and anorexia, and also general lassitude, are often observed 
after the use of large doses of sarsaparilla root. These 
symptoms are identical with those which have been noticed 
after the experimental therapeutic employment of smila- 
cin, the active principle of the root. 

Folia Toxicodendri. 

The officinal fresh leaves of the poison-sumach contain 
a yellowish-brown juice which is also found in the tincture 
of rhus toxicodendron. In recent times this agent is but 
rarely prescribed. It is, nevertheless, necessary to call 
attention to the fact that the fresh leaves and the tincture, 



EVACUANTS. 20/ 

in doses not above the maximum limit, may produce, in 
certain persons, pains and gastroenteric symptoms, also 
o-iddiness, deafness, delirium, and anaesthesia, and condi- 
tions simulating paralysis. In addition to these symptoms, 
there not infrequently appear, after the external applica- 
tion of the fresh leaves or the extract, violent itching-, an 
erysipelatous redness and swelling of the skin, and also a 
vesicular or measles-like eruption, itching intensely, and 
disappearing only after some days, with desquamation. 
The emanations from the living plant are said to produce 
the same effect. 

IV.— EXPECTORANTS. 

Ammonii Chloridum. 

Sal ammoniac, introduced in small quantities into the 
stomach, produces no unpleasant effects. Nevertheless, the 
long-continued use of the drug in doses of one to two 
grams (gr. xv.-3ss.) may give rise to derangements of 
digestion and loss of appetite. After taking four to eight 
grams ( 3 i.- 3 ij.) and more, daily, Jacquot 1 observed diar- 
rhoea and attacks of abdominal colic, and also nausea and 
vomiting. 

Antimonii Sulphuretum. 

The sulphuret of antimony, which is sometimes used as 
an expectorant and resolvent, cannot be absorbed from the 
stomach, on account of its insolubility in water and dilute 
acids. It is, however, partially dissolved by the alkaline 
intestinal juices, as was proved by the experiments of L. 
Lewin, 2 and may then, as practical experience teaches, 
develop the complete action of antimony, as manifested by 
the production of vomiting and diarrhoea. The intensity 
with which this incidental action occurs depends upon the 

1 Jacquot: Schuchardt's Arzneimittellehre. Braunschweig, 1858, p. 390. 

2 L. Lewin, Virchow's'-Archiv, Bd. 74. 



208 . INCIDENTAL EFFECTS OF DRUGS. 

quantity of the drug dissolved in the intestines, which 
varies with the degree of fulness of the stomach, for when 
this organ is well filled, the drug is carried, with that por- 
tion of the contents which escapes absorption, into the in- 
testines, whence it may be discharged with the fasces. 
The incidental effects are therefore most intense when 
the stomach is nearly empty. 

Radix Senega. 

Isolated statements occur in the older literature of the 
subject, concerning the incidental effects which appear 
after the use of senega. In some cases, after doses of i to 
1.5 grams (gr. xv.-xxiv.) the drug is said to have caused a 
sensation of tickling and burning in the throat, increased 
flow of saliva, oppression over the stomach, nausea, vom- 
iting and anorexia, symptoms which were followed by 
colicky pains and diarrhoea. Attention has recently been 
called to the fact that a drug is now and then sold as 
senega, even by respectable houses, which fails to produce 
the peculiar effects of this drug, and is not botanically 
identical with it. 

V.— ANTIPARASITICS. 

Balsamum Peruvianum. 

Unlike other balsamic agents, balsam of Peru has been 
but rarely found to produce incidental effects. Mogling 1 
has recently published an observation of the appearance 
of urticaria, lasting four days, after one inunction with this 
drug. After one evening rubbing upon his own person, 
on the arms, shoulders and breast, for the cure of scabies, 
about eight grams (3ij.) of the balsam, he was affected 
with an uncomfortable feeling of heat of the body, and a 
burning sensation in the lungs, which was followed by a 

1 Mogling, Berliner klin. Wochenschrift, fS8o, p. 557. 



EVACUANTS. 



209 



spell of coughing-. On the following morning, there ap- 
peared on the inner surface of the knee and on the shoul- 
ders, redness of the skin in patches, attended with intense 
itching. The latter symptom disappeared during the day, 
but returned at night. It originated in closely aggregated 
wheals, seated upon the thighs, sides of the abdomen, upper 
arms, and shoulders. At the same time he felt chilly and was 
nauseated, without his bodily temperature being elevated. 
Two days later, after inunctions with lard had been occa- 
sionally used with good results, for the relief of the local 
and general symptoms, and after the urticaria had succes- 
sively attacked also the face, neck, back, forearms, fore- 
legs, and the backs of the feet, he relieved himself from the 
trouble by means of a bath, and leaving off the woollen 
undershirt which he had worn during the four days of his 
illness. 

According to Mogling, the congestion of the lungs may 
have been due to a taking-up of the drug by those organs, 
or, in view of the fact that he had long suffered from bron- 
chitis and haemoptysis, it might be regarded as the result 
of an injurious action upon a " locus minoris resistentise." 

Less extensive eczematous eruptions upon the skin are 
occasionally observed as consequences of a local irritant 
action of balsam of Peru (perhaps only when a bad prepa- 
ration is used), on places where it was applied for the cure 
of scabies. Such an occurrence may cause the observer 
to believe that scabies is still present, after the insects 
have long since been killed. 

Styrax Liquidus. 

Unna 1 observed albuminuria in patients suffering from 
scabies, who were being treated with styrax ointments. 
It occurred nine times in one hundred and twenty-four 
cases. A relatively large quantity of albumen suddenly 

1 Unna, Virchow's Arch., Bd. 74. 
14 



2IO INCIDENTAL EFFECTS OF DRUGS. 

appeared in the urine, and as rapidly disappeared. Unna 
believes that the tolerably large quantity of the balsam 
which is absorbed by the skin is the cause of this phenom- 
enon. The passage of substances with a higher atomic 
weight through the walls of the renal capillaries, is said 
to make them permeable for albumen also, for a varying 
period. 

Rhizoma Filicis. 

Extract, filicis maris cetherenm. 

The root of male fern or its extract, which is much em- 
ployed in large doses for the destruction of tape worms, 
has a disagreeable biting taste, and sometimes causes pains 
in the stomach and abdomen, nausea, vomiting, and diar- 
rhoea. It is probable that the bad quality of the prepara- 
tion employed is to blame for the production of these 
symptoms. 

Cortex Radicis Granati. 

After the administration of the bark of pomegranate 
root, in doses such as are usually given for the cure of 
tape-worm, particularly when the remedy is taken with 
too short intervals between the doses, there frequently ap- 
pear nausea and vomiting, abdominal pains, and diar- 
rhoea. Dizziness, a feeling of weakness, or temporary 
trembling of the limbs, are also not infrequently noticed 
after its use. According to Merat, 1 the bark causes an in- 
crease in the secretion of urine. These symptoms disap- 
pear immediately after the use of the agent is suspended. 

The variations in the mode of action of pomegranate bark 
are dependent upon the age of the preparation, since only 
the fresh root is capable of producing curative effects. 
In the use of a reliable preparation, small doses should be 
prescribed, and, since its action is exerted -in a very short 

1 Merat, Gazette des hopitaux, 1845, p. 115. 



EVACUANTS. 211 

time, incidental phenomena are rare, and of only limited 
duration when they occur. 

Santoninum. 

Wormseed, as well as its derivative santonin, almost al- 
ways produces undesired effects by its administration in 
medicinal doses. 

Neither santonin, which is insoluble in water, nor the 
soluble santonate of sodium, produces a red color when 
mixed with alkalies. This occurs, however, if they are 
first dissolved in alcohol, and then treated with alkalies. 
In the human body, santonin undergoes changes similar 
to those produced by alcohol in the drug. After it is 
taken in any form, and in small doses, 0.2 gram (gr. iij.) 
and more, in two or three hours the urine shows a yel- 
low color, as if curcuma or chrysophanic acid had been 
added to it. White paper or linen dipped into it shows 
yellow spots when dried, a circumstance to which Martin l 
first called attention. If alkalies, such as soda-lye, ammo- 
nia, or an alkaline carbonate, are added to such urine, it 
becomes of a cherry-red color. The red color disappears 
spontaneously after from thirty to thirty-six hours, in con- 
trast with the urine passed after taking rhubarb, the red 
color of which, produced by alkalies, is permanent, accord- 
ing to J. Munk. 2 According to this author, still further 
differences between these two kinds of urine are shown by 
the fact that the red color of the rhubarb-urine dis- 
appears under the influence of reducing agents (zinc-dust, 
sodium-amalgam), while that of santonin-urine resists 
their action, and also that baryta and lime-water added to 
rhubarb-urine throw down the chrysophanic acid with the 
deposit (the red color of which is not removed by wash- 



1 Martin: Buchner's N. Repert. f. Pharmacie, Bd. ii , 1853, H. 5. 

2 J. Munk, Virchow's Archiv, 1878, p. 136. 



212 INCIDENTAL EFFECTS OF DRUGS. 

ing), while in alkaline santonin-urine, under the same 
treatment, the pigment remains in solution. 

Santonin-urine turns the plane of polarization to the 
the left, as L. Lewin accidentally discovered. The changes 
which santonin undergoes in the body are unknown. 
Mialhe 1 believes that an oxidation-product, with the qual- 
ities of a weak acid, is produced. Its elimination by the 
urine can be demonstrated two or three days after it is 
taken, even in doses of only 0.2 to 0.4 gram (gr. iij.-vi.). 
If santonin-urine undergoes decomposition, the carbonate 
of ammonium which is produced, causes it to take on a 
red color, which may, under certain circumstances, such 
as the presence of vesical catarrh, lead to its being mis- 
taken for bloody urine. 

In some cases, strangury and itching in the urethra have 
been noticed after taking santonin. 

Almost as constant as the changes in the urine are certain 
disturbances of the sense of sight, which show themselves 
after even small doses of santonin. They manifest them- 
selves principally as yellow-seeing (chrqmatopsia), and 
sometimes last several hours. This phenomenon was first 
observed by Itzstein, and later by Spencer-Wells, but has 
been most carefully studied by Rose. 2 According to him, 
there occasionally appears before the real chromatopsia, 
after large doses of santonin, a violet color of the field of 
vision, which increases in intensity with the darkness of 
of the objects looked at. All lighter bodies, windows, pa- 
per, etc., seem really yellow. Red and blue often appear 
in their complementary colors, orange and green, so that 
carmine-red objects seem pale, madder-red of a bronze 
color, and the sky and other blue objects green. This is, 
however, not always the case, and one also sometimes ob- 
serves that, after taking santonin, red seems violent, or 



1 Mialhe, Comptes rendus, xlvii., p. 413. 

2 Rose, Virchow's Archiv, Bd. xvi., p. 233 u. Bd. xviii., p. 15. 



EVACUANTS. 213 

light and dark objects are taken by one person for orange, 
and by another for green. 

This phenomenon is not due to a coloring of the ocu- 
lar media by a product of decomposition of santonin, 
as was formerly believed to be the case, in analogy with 
the action of the coloring-matter of the bile in icterus, but 
is, according to Rose, the result of a nervous change in 
the retina. M. Schultze 1 adopts the view that the macula 
lutea experiences an increase in its yellow pigment 
through the action of santonin, and that, therefore, chro- 
matopsia takes place. The entire absence of santonin in the 
ocular media, as well as the failure thus far to demonstrate 
it chemically in the retina, renders improbable a direct 
action of this substance upon the parts which receive the 
light, but does not, according to Herman, 2 exclude the 
possibility of its occurrence, on account of the fact that 
the changes are so slight, and, therefore, the quantity of 
the active substance is so small that it may entirely escape 
detection. 

Among other changes in the eye, Martin observed an 
increased secretion of tears and a feeling of pressure, and 
others noticed spots before the eyes. While Rose de- 
nies the occurrence of amblyopia and accommodative dis- 
turbances, other authors, such Bianchi and Cogliesi 3 re- 
port amaurosis lasting two months and a half, in children, 
after medicinal doses. 

Besides the eyes, the stomach is also affected by santo- 
nin, in many persons. Thus Martin experienced nausea 
after 0.4 gram (gr. vi.), and Rose observed vomiting after 
it. With these symptoms may- be associated rumbling in 
the abdomen and eructation. 

Rose has also reported the occurrence of nervous symp- 



1 M. Schultze: Ueber d. gelben Fleck d. Retina. Bonn, 1866. 

2 Hermann: Lehrbuch der Toxikologie, Berlin, 1874, p. 384. 

8 Bianchi Cogliesi, Refer, in Husemann, Pflanzenstoffe, Berlin, 1871, p. 92S. 



2I 4 



INCIDENTAL EFFECTS OF DRUGS. 



toms of a central origin, such as olfactory and gustatory 
hallucinations, headache, and a kind of spiritual depres- 
sion, collectively described as "santonin-intoxication." 

Affections of the skin are very rarely produced by the 
use of santonin. Sieveking 1 has described a case of this 
kind. A child, who was given 0.18 gram (gr. iij.) of san- 
tonin for the cure of helminthiasis, vomited soon after 
taking it, and there then appeared an urticaria over the 
entire body, which, however, soon passed off. When 0.18 
gram (gr. iij.) was again administered, general urticaria 
again showed itself, and the entire skin, particularly on the 
eyes, nose, and lips, became so much swollen and so cede- 
matous that the face was totally unrecognizable. Saliva- 
tion was also present. The sensorium was not affected. 
After a warm bath, all the symptoms disappeared in an 
hour. 

Benzolum. 

J. Munk 2 found, by experimenting upon himself, that 
benzole possesses a disagreeable, burning taste, and pro- 
duces an almost caustic effect upon mucous membranes. 
Beginning with twenty-five, he took as much . as fifty 
drops, in twenty-four hours, and afterwards experienced 
a feeling of fulness, weight, and burning in the epigas- 
trium, and slight headache, while no marked effect was 
produced upon either pulse or respiration. According to 
Simpson, 3 the inhalation of benzole for the purpose of 
producing anaesthesia, is followed by unbearable roaring 
in the head, and Richardson noticed muscular spasms, dif- 
ficulty of respiration, and convulsions, after using the drug 
in this manner. 

A portion of the benzole is eliminated by the stomach 
in the form of a gas, as shown by the fact that eructations 

1 Sieveking, British Medical Journal, Feb., 1871. 

2 J. Munk, Pfluger's Archiv, Bd. xii., p. 147. 

3 Simpson, Monthly Journal Medical Science, 1848, April. 



EVACUANTS. 21 5 

occur soon after beginning the use of the agent, and last 
eight hours longer, having the odor and taste of coal-tar. 
Another portion enters into an organic group of atoms, 
and forms with it the "phenol-forming substance." 

After the external application of this agent for the de- 
struction of pediculi on the genital organs, care must be 
taken that it does not get in between the thighs and the 
scrotum. On this and other similarly sensitive parts, it 
produces intense pain, lasting several minutes, which is 
followed by a more or less extensive erythema. 

ACIDUM PlCRICUM. 

Picric acid, which was formerly used as an astringent 
and tonic, and also as an anthelmintic, sometimes produces, 
after being used internally, as Seitz 1 has stated, an icteric 
discoloration of the skin and conjunctiva. 



VI.— SUDORIFICS. 
Folia Jaborandi. 

After the use of jaborandi, made from the leaves of Pi- 
locarpus pinnatus and simplex, the majority of observers 
report a series of objectionable incidental effects as atten- 
dants upon the normal action of the drug. The latter 
consists, as is well-known, in the occurrence of sweating, 
accompanied by a subjective feeling of warmth, in from 
ten to twenty minutes after taking, e. g., four grams (fl. 
3 i.) of an infusion of the leaves. It appears first on the 
skin of the abdomen and chest, later in the face, and finally 
on the upper and lower extremities, and lasts from about 
two to four hours. The secretion of a viscid saliva, which 
occurs simultaneously, or begins a little sooner, lasts the 
same length of time. According to Riegel, 2 the average 

1 Seitz, Deutsche Klinik, 1855, 40. 

2 Riegel, Berliner klin. Wochenschr., 1875, No. 46. 



2i6 INCIDENTAL EFFECTS OF DRUGS. 

loss of weight after the sweating is 750 to 1,000 grams, 
(one to two pounds), but may amount to more than two 
kilograms (four pounds). A short time after taking the 
drug, the pulse becomes fuller, more frequent and softer, 
and later it often becomes smaller, with diminished force 
of the heart's action, facial pallor, and a subjective feeling 
of coldness. 

Among the incidental effects which have been observed, 
mention should first be made of the vomiting which oc- 
curs from one-half to one hour after taking the drug, and 
which is always preceded by prolonged nausea. It is 
extremely annoying and exhausting to the patient, lasts 
for a long time, and may readily lead to dangerous col- 
lapse. In forty-one experiments, Riegel observed it 
eighteen times, and ten times nausea without vomiting. 
Lohrisch, 1 in thirty cases, saw violent vomiting twelve times, 
and nausea and inclination to vomit twenty-two times. The 
nausea showed itself sometimes immediately, sometimes 
half an hour, and even later, after taking the medicine. 
Bardenhewer 2 attributes the nausea and vomiting to the 
fact that, in consequence of its free secretion, small quanti- 
ties of saliva are swallowed, and in this manner the very 
sensitive mucous membrane of the palate, the throat, etc., 
is irritated. Riegel accepts this explanation for only a 
part of the cases, as he witnessed the occurrence of vomit- 
ing also in patients who expectorated the saliva, instead of 
swallowing it. 

After the nausea and vomiting, increased frequency of 
micturition is the most common symptom, occurring in 
about forty per cent of the cases. It appears so suddenly, 
and the desire is so great, that the patients are absolutely 
unable to resist it. Now and then a burning pain in the 

1 Lohrisch, Berliner klin. Wochenschrift, 1875, No. 18, and Inaug. Dissert., 
Berlin, 1875. 

2 Bardenhewer : Ueber die therapeut. Wirkung des Jaborandi, Bonn, 1875. 



EVACUANT^. 



217 



urethra and small of the back is also noticed, which is so 
intense as to draw loud cries of suffering from the patients. 

The disturbances of vision so frequently noticed, to 
which Martindale first called attention, are also worthy of 
mention. The patients state that they are unable to see 
distinctly, because there seems to be a veil before their 
eyes. A few authors claim to have also observed dilata- 
tion of the pupils in these cases, but Riegel was not able 
to confirm this statement. 

In addition to these incidental effects, there also occur 
not infrequently hiccough, dizziness, headache, with a 
kind of stupefaction, and, in some cases, a more or less 
intense chilliness, appearing near the close of the sweating 
stage, and also gastric and abdominal pains. After the 
cessation of the sweating, these symptoms also come to an 
end. In very weak persons, collapse without vomiting 
is occasionally observed. 

PlLOCARPINUM MURIATICUM. 

After the discovery of the pharmacological qualities of 
jaborandi, numerous experiments were undertaken with a 
view to obtain its active principle in the hope that, by using 
it instead of the leaves, the obnoxious incidental effects 
might be avoided. Merk succeeded in obtaining the pure 
alkaloid, or its hydrochloric acid compound, in the form of 
a crystalline substance, with a slightly bitter and astrin- 
gent taste, soluble in an equal quantity of water. 

Although it has been found in the course of time that 
the use of this agent is also attended with a number 
of unpleasant symptoms, its quality of developing its 
activity from the subcutaneous connective tissue as a 
starting-point, causes it to present such great advantages 
over the leaves of jaborandi, that the latter must be placed 
much below pilocarpia as a diaphoretic. According to 



2i8 INCIDENTAL EFFECTS OF DRUGS. 

the experiments of Weber, 1 one ccm. of a two-per-cent 
solution of the muriate of pilocarpia is equal to an infusion 
of five grams (gr. lxxv.) of jaborandi leaves in one hundred 
and twenty grams (fl. § iv.) of water. The quantity of 
saliva secreted after an injection of pilocarpia varies, 
according to Losch, 2 with the individuality of the patient. 
The saliva itself is tough, viscid, and often as thick 
as the white of egg. The occurrence of salivation follows 
immediately upon the secretion of the sweat. In this 
respect also, the individuality of the patient plays a role, as 
is shown by the fact that some persons are bathed in sweat, 
while others transpire but slightly, after the same dose. 
Rigors are now and then observed during the sweating. 
Intimately associated with these phenomena is an increase 
in the frequency of the pulse, to the extent of thirty or forty 
beats in a minute. The patients often complain of palpi- 
tation of the heart, and very sensitive persons of a feeling 
of anxiety, which, however, speedily passes away. 

Vomiting also occurs, and becomes very violent when it 
once begins. According to the statement of Losch, this 
symptom occurs once in five times in women, but only 
once in ten times in men. It is usually followed by col- 
lapse. In children, in addition to vomiting, Demme 3 saw 
weakness approaching fainting, pallor of the lace, and dis- 
tressing hiccough. A burning sensation in the urethra or 
glans penis was also frequently noticed, usually associated 
with frequent micturition. Federschmidt 4 also observed 
dysuria in two instances. During the secretion of sweat 
and saliva, the patients sometimes complained of a feeling 
as if their bladders were full, and unable to empty them- 
selves. When injections were again practised upon the 
same persons, these abnormal sensations failed to appear. 

1 Weber, Centrallblatt f. d. medicin. Wissenschaften, 1876, No. 44. 

2 Losch, Deutsches Archiv f. klin. Medicin, xxi., p. 258. 

3 Demme, Centralzeitung fur Kinderheilkunde, 1877, No. 1. 

4 Federschmidt : Zur Wirkung des Pilocarpin muriatic, Erlangen, 1877. 



EVACUANTS. 

A disturbance of vision, characterized by mistiness* 
which frequently occurs, is also worthy of mention in this 
connection. In some persons with normal range and clear- 
ness of sight, this becomes so intense that, as Losch states, 
they are unable to read large print six inches from the 
eyes. This phenomenon also presented itself in cases in 
which there was no increase in the lachrymal secretion. 

The most unpleasant of all the incidental effects is, how- 
ever, the collapse, which appears both during the stage of 
secretion, and after it, even in robust persons. The greatest 
attention must be paid to this symptom during the use of 
pilocarpia, because, if the possibility of its occurrence be 
ignored, a fatal result may easily take place. The heart 
must also be watched with the greatest care, particularly 
in persons with lesions of this organ, on account of the 
well-established enormous acceleration of its action, which 
is often attended with irregularity. 

An observation of Ranneft 1 may also be mentioned in 
this place. After the subcutaneous injection of 0.02 gram 
(gr. -J-) of muriate of pilocarpia in a patient with uraemia, 
there appeared on the next morning, after the diaphoresis 
had passed off, a swelling of the submaxillary glands, to 
the size of a fist, and also of the parotids and tonsils, with 
fever. Under the use of atropia these phenomena passed 
off in the course of a day. 

Great danger is incurred by the untimely use of pilocar- 
pia in eclampsia. Sanger reports three such cases, in 
which the injection of 0.02 gram (gr. -3) of pilocarpia was 
followed by oedema of the lungs. In one case, life was 
saved by the antidotal employment of 0.0006 gram (gr. T -i~g-) 
of atropia hypodermically, but death occurred in both the 
others. Sanger explains this injurious action of the drug 
by the deficient expectoration of the masses of mucus 

1 Ranneft, Jahresber. f. d. ges. Medicin von Virchow-Hirsch, 1877, ii-> P- 437- 

2 Sanger, Archiv f. Gynakolog., Bd. xiv., H. 1. 



220 INCIDENTAL EFFECTS OF DRUGS. 

which are formed under its influence, and their entrance 
into the lungs. Expectoration cannot be performed, be- 
cause unconsciousness and loss of reflex activity are pro- 
duced by the eclamptic attacks. 

The fact that these abnormal phenomena were observed 
by a number of investigators, although they employed the 
same preparation, excludes the hypothesis that they were 
due to the quality of the drug. It seems probable that a 
certain disposition of the affected persons, and, perhaps, 
in some cases, also the improper doses of the agent em- 
ployed, are responsible for their occurrence. As regards 
the latter factor, both Leyden 1 and Curschmann 2 state that 
the occurrence of collapse may be prevented by a very 
gradual increase of the dose. In view of previous experi- 
ence, it must be confessed that it is beyond our power to 
prevent the occurrence of hurtful incidental effects, and 
we must, therefore, content ourselves with combating 
them as soon as they appear. 

Atropia occupies the most important position as an 
appropriate remedy for this purpose, because it puts an 
end to both the sweating and the salivation, and also to the 
painful sensations, and arrests the vomiting. It should be 
administered either subcutaneously — five or ten drops of 
the following solution : Atropine sulphat., o.i ; Aquas dest., 
20.0 (gr. iss. : fl. 3 v.) — or internally, twenty to thirty drops 
every two hours of this solution : Atropiae sulph., o.oi ; 
Aquae dest., 20.0 (gr. 1 : fl. 3 v.) until the symptoms are 
relieved. Collapse should be prevented by the adminis- 
tration of stimulants. Demme (1. c.) says that he avoids 
the majority of the hurtful incidental effects by giving 
brandy before making the injection. It is, as a rule, 
advisable to administer the pilocarpia before rather than 
after the principal meal, and, in view of the numerous 

1 Leyden, Berliner klin. Wochenschrift, 1878, No. 27 u. 28. 

2 Curschmann, eod. loco, No. 25. 



EMOLLIENTS. 221 

observations of collapse occurring in patients with cardiac 
valvular lesions, to regard diseases of the heart as contra- 
indications to the use of the drug. Ohms 1 also regards 
pilocarpia as contra-indicated in cases of gastric ulcer and 
in typhoid fever, because hemorrhages may be easily ex- 
cited, in consequence of the great dilatation which the 
vessels experience under the influence of the drug. 

EMOLLIENTS. 

Glycerinum. 

The healing powers of glycerin upon wounds, which 
were particularly demonstrated by the experiments of 
Demarquay, 2 frequently fail to show themselves, or are 
even supplanted by directly opposite effects. This failure 
on the part of the agent is attributable to the impurity of 
the preparation employed. If it is placed in an impure 
condition upon wounds, upon eruptions on the skin, etc., 
there occurs a burning sensation at the point of applica- 
tion, lasting several hours, and a feeling of increased heat. 
At the same time, the affected part becomes swollen. 
Moist eruptions secrete more freely, and new pustules 
are formed under certain circumstances. 

Absolutely pure glycerin applied to wounds produces 
only temporary burning, which is probably due to its 
hygroscopic powers. In using this agent, care must be 
taken that its specific gravity lies between 1.23 and 1.25, 
as prescribed by the Pharmac. Germanica. More highly 
concentrated preparations should not be used therapeuti- 
cally, on account of their irritating properties. 

Oleum Jecoris Aselli. 
The peculiarly offensive odor and taste of cod-liver oil 

1 Ohms, Petersburger medic. "Wochenschrift, 1878, No. 6, p. 50. 

2 Demarquay : De la Glycerine, Paris, 1867. 



222 INCIDENTAL EFFECTS OF DRUGS. 

produce at first, in different persons, usually adults, nausea, 
and even vomiting, during and after its administration, 
which are not repeated, however, if it is used for a long time. 
If too large doses are taken, diarrhoea occurs. Cod-liver 
oil sometimes produces eczema also, when used for several 
days. This observation of S. Bennett 1 is explained by the 
fact that, after large doses of the oil, the skin emits the 
peculiar odor of the volatile fatty acids in the oil. These, 
during their circulation in the body, reach the skin also, and 
there produce eruptions, probably by direct irritation. 
These are, according to Duclos, 2 always of a vesicular 
nature, and spread over the entire body. 

RUBEFACIENTS AND VESICANTS. 

Chlorinum. 

Chlorine gas is irrespirable. Even when highly diluted 
with atmospheric air it is an energetic irritant to the mu- 
cous membrane of the air-passages, causing increased se- 
cretion of these parts, nasal catarrh, cough, oppression of 
the chest, and symptoms of genuine bronchitis. 

If the gas acts upon the skin, there soon occurs an ery- 
thema, with itching, which disappears in a short time, 
with desquamation. Even in a diluted condition it pro 
duces pricking and itching of the skin ; according to Schu- 
chardt, 3 this organ is rendered more sensitive, and a 
papular eruption may appear, which ends in branny des- 
quamation. 

Cantharides. 

After the internal administration of cantharides or its 
tincture, in medicinal doses, a number of incidental effects 

1 Bennett : Treatise on the Oleum Jecoris Aselli, London, 1841, pp. 16 arid 47. 

2 Duclos, Journal de Medecine, Sept.-Novembre; 1846. 

3 Schuchardt: Arzneimittellehre. Braunschweig, 1858, p. 198. 



RUBEFACIENTS AND VESICANTS. 



223 



manifest themselves, varying in intensity according- to the 
individuality of the affected person. A burning sensation 
is experienced in the primae viae. After a time there oc. 
cur urgent desire to urinate, a burning feeling in the 
urethra, and frequent and painful erections. The last 
phenomena may develop into dangerous symptoms, after 
prolonged use of small doses, or after their increase with- 
out exceeding the ordinary limits. The mucous mem- 
branes of internal organs become the seat of more or less 
violent inflammation, and the consecutive symptoms of 
these changes show themselves, on the part of the stomach 
and intestines, in the form of nausea, vomiting, and diar- 
rhoea, and on the part of the urinary passages as increased 
frequency of micturition, attended with the discharge of 
urine, sometimes containing blood, or albumen or morpho- 
logical constituents, and on the part of the genital organs 
in the form of painful chordee. 

The skin also sometimes manifests exanthematic disor- 
ders, in the form of erythematous or papular eruptions. 

Of more importance than these effects of the internal 
administration of cantharides is a knowledge of those 
which appear after its external application. These changes, 
which correspond to those already described, may be 
produced by the application of a Spanish-fly blister, in 
consequence of the absorption of the active principle of 
cantharides. Thus Ledelius, 1 among others, noticed vom- 
iting, strangury, and fever, after the application for three 
hours of a blister. These symptoms produced by absorp- 
tion are the more intense, the more the portion of skin to 
which the agent is applied deviates from its normal condi- 
tion. 

The treatment of these symptoms consists in the imme- 
diate removal of the plaster, and cleansing the skin with 
soap. Mucilaginous beverages should be administered, 



1 Ledelius, Refer, in Wibmer, Wirkungen der Arzneimittel, Bd. iii., p. 252. 



224 INCIDENTAL EFFECTS OF DRUGS. 

to counteract the phenomena of irritation of internal 
organs. 

Faba Anacardii. 

The Anacardium bean, popularly known as Cashew nut, 
contains within its pericarp a reddish-yellow substance, 
cardol, soluble in ether, alcohol, etc., which was recom- 
mended by Frerichs as a vesicant, under certain circum- 
stances preferable to cantharides. The cardol prepared 
from Anacardium occidentale is known as cardoleum vesi- 
cans, that from Semecarpus anacardium as cardoleum 
pruriens. The latter is unfit for use on account of its 
property of producing dermatitis and even erysipelas. 
But after the application of anacardium occidentale also, 
the effect is often not a limited one, extensive inflammatory 
oedema and eczema being produced on remote parts of 
the body, e. g., the face. 

While this agent is but seldom employed by physicians, 
the anacardium bean is much used among the laity, and 
therefore frequently produces diseases of the skin. Thus 
E. Schwerin 1 found in the person of a woman who had 
placed one-half of a bean in her ear, to relieve toothache 
and pain in the face, an erysipelas of enormous extent. 
The face was bloated, both eyelids infiltrated, and the 
ear, the cheek, and the front of the neck, as low down as 
the clavicle, swollen and reddened. The external auditory 
canal, the external ear, and the adjacent portions of skin 
were covered w T ith vesicles. Recovery took place in a 
few days. 

In another case, in order to relieve pains in the chest, 
an anacardium bean was perforated longitudinally, placed 
upon a string and hung around the neck in such a manner 
that it lay over the manubrium sterni. Two days later, an 

1 According to a previously unpublished observation which was kindly placed 
at my disposal. 



RUBEFACIENTS AND VESICANTS. 225 

erysipelas had developed, which covered the whole front 
of the chest, the mammae, and the region of the shoulder 
as far up as the lower jaw, and presented a large number 
of vesicles upon its surface. 

According to Bazin, 1 the oil expressed from the pericarp 
of the bean, when applied to the skin, also sometimes 
produces, within from six to twenty-four hours, one or 
more vesicles, the contents of which soon become purulent. 

Cortex Mezerei. 

Mezereon, which still occasionally finds employment as 
a vesicant, or for the application of superficial issues, 
produces vesicles upon the skin which may develop into 
ulcers. These are very painful, heal with extreme slow- 
ness, and are often accompanied by a pustular eruption 
around their edges. 

After the appearance of the inflammatory phenomena, 
symptoms of systemic poisoning or even death may occur 
in consequence of the absorption of the drug. Such a case 
was studied by Pluskal. 2 Headache, dryness of the throat, 
cough, and fever appeared, and finally death took place, at- 
tended with loss of consciousness and convulsions. 

SUMMITATES SABINE. 

The use of the powdered tops of savine for the cauteri- 
zation of condylomata, sometimes causes such intolerable 
pain that the use of the remedy must be abandoned. 

After the internal administration of small and medium 
doses (0.3 to 0.8 grams) (gr. ivss.-xiiss.) as an emmenagogue, 
there occur di'gestive disturbances, and sometimes also 
vomiting and diarrhoea, strangury, and during menstrua- 
tion, excessive loss of blood. In pregnant women, the too 



1 Baz n, 1. c, p. 119. 

2 Pluskal, Oesterreichische medic. Wochenschrift, 1842, No. 18, and 1S44, 
No. 50. 

J 5 



226 INCIDENTAL EFFECTS OF DRUGS. 

prolonged use of small or of too large doses may induce 
abortion. 

The action of Oleum Sabinae is more intense than that of 
the tops. 

Chrysarobinum. 

Goa-Powder. 

A secret remedy, " Araroba-powder, or Goa-powder," 
has long been employed in the treatment of skin diseases 
in England, Brazil, and the East Indies. The tree which 
furnishes the powder is most common in the province of 
Bahia. The araroba, in the form of a sulphur-yellow 
powder, is found in the crevices and cavities which traverse 
the tree in the direction of its transverse diameter. 1 Ac- 
cording to a previous analysis, the powder should contain 
eighty-four per cent of chrysophanic acid. Liebermann 2 
showed, however, that the substance obtained from goa- 
powder by extracting it with benzole, was not chrysopha- 
nic acid, but a body of different chemical composition, 
which he called chrysarobin. It may be transformed into 
chrysophanic acid by the addition of potash-lye and the 
admission of air. 

Balmanno Squire 3 first employed this agent in the form 
of an ointment, in the treatment of psoriasis, and after- 
wards of eczema, acne, etc., with good results. Numerous 
therapeutical experiments were afterwards made in Ger- 
many with chrysarobin. The ointment is usually applied 
upon the skin after the psoriatic scales are removed, either 
mechanically or by chemical means (green-soap, etc.). 

All the experimenters who used chrysarobin report 
unpleasant incidental effects after its application, which 
appeared as local and general symptoms. These have 

1 Vierteljahrschrift f. Dermatolog. u. Syphilis, vi., 1879, p. 385. 

2 Liebermann, Berichte der deutsch. chem. Gesellschaft, Jahrg. xi., p. 1603. 

3 Balmanno Squire, British Medical Journal, May and November, 1877. 



RUBEFACIENTS AND VESICANTS. 227 

been best described by Kaposi. 1 If chrysarobin is 
rubbed upon psoriatic patches, there appears, early in 
some persons, later in others, an inflammation at the 
point of application, which may spread over a large extent 
of the healthy skin. Many individuals seem especially 
predisposed to this accident, and in such cases the inflam- 
mation increases inordinately in intensity and extent. The 
face and the genitals seem to possess a peculiar sensitive- 
ness to chrysarobin ointment. 

Three forms of inflammation occur, according to Ka- 
posi : 

1. A diffuse inflammatory redness and swelling. In 
many cases this appears as a halo of varying breadth around 
each patch of psoriasis, after from four to six in some, in 
others after from eight to fifteen applications. If no more 
inunctions are made, this redness disappears after from ten 
to fourteeen days, with desquamation of the epidermis. 
But in spite of the cessation of the applications, the inflam- 
mation and swelling often spread still further, and cause 
pain, fever, sleeplessness, glandular swelling, etc., in short,, 
the general symptoms which are usually observed after a 
diffuse dermatitis. 

2. The inflammation may also manifest itself by the ap- 
pearance of pin-head sized, reddish-brown, firm papules, 
some of which also present vesicles and pustules. They 
correspond to the openings of the follicles. The patient 
complains of annoying itching and burning. 

3. Painful furuncles may also be developed. 

For the relief of the pain and the inflammation, the ap- 
plication of cold-water compresses has been recommended. 
In order to prevent these irritations of the skin, Neumann 
advised the protection of the parts around the diseased 
patches by strips of adhesive plaster. Others believe that 
the unpleasant effects of the drug may be avoided by 

1 Kaposi, Wiener medicin. Wochenschrift, 1878, No 44. 



228 INCIDENTAL EFFECTS OF DRUGS. 

gradually increasing- the proportion of chrysarobin in the 
ointment. Kaposi advises against the use of the agent on 
the face, and directs that it be employed on the genitals 
only after careful isolation of the adjoining folds of skin, 
and that the application be suspended, as soon as inflam- 
matory areola? have formed around the patches of psoria- 
sis. 

A discoloration of the tissues which come into contact 
with the drug nearly always occurs as an accessory symp- 
tom of the above-mentioned incidental effects. The nor- 
mal skin, as well as the nails, take on a reddish or violet- 
brown appearance, and the hair becomes of a golden-yellow 
or of a variegated greenish color. If soap is used upon 
parts thus deprived of their normal color, the reddish- 
brown color is changed into dark violet, in consequence of 
the action of the potash upon the chrysarobin. This trans- 
formation of color is most marked on the inflammatory 
ring which forms around the psoriatic patches. The under- 
clothing of the patients, like the skin, becomes covered 
with spots of a more or less purple-brown or violet color, 
which are very hard to remove. 

Acidum Pyrogallicum. 

Pyrogallic acid was introduced into the treatment of 
skin diseases by Jarisch. 1 Only insignificant incidental 
effects show themselves after its employment. Applied to 
psoriatic patches or the normal skin, it produces a brown 
discoloration. On the extremities it excites localized in- 
flammation, which may lead to epidermic desquamation 
and the formation of vesicles. When applied to hard, in- 
filtrated patches, the ointment produces deep losses of 
tissue, reaching down to the corium. The scars left behind, 
after cauterizing lupus nodules with pyrogallic acid, are 
smooth, white, and flexible. Jarisch, after the use of the 

1 Jarisch, Wiener medic. Jahrbiicher, 1878, H. iv. 



RUBEFACIENTS AND VESICANTS. 



229 



acid in eczema marginatum, observed pain lasting several 
days, and increasing when the dressings were changed. 

Instigated by the success obtained by Jarisch, Neisser 1 
also tried pyrogallic acid in the case of a man afflicted 
with psoriasis universalis. For purposes of comparison the 
right arm and leg, and the back, were energetically rubbed 
with unguentum Rhei (Extr. Rhei spirit, in the form of a 
twenty-per-cent ointment), the left side and the breast with 
pyrogallic acid, and finally smeared with a thin layer of 
the ointment, and then the whole body was covered with 
rubber paper, which was secured by roller bandages. A 
few hours after this operation there appeared rigors, diar- 
rhoea, and vomiting, which lasted three days, until death 
occurred in collapse. The urine contained the coloring 
matter of the blood. The autopsy revealed as the causes 
of death, decomposition of the blood, nephritis hsemoglo- 
binica, and a disseminated fatty degeneration of the mus- 
cular tissue of the heart. 

The majority of the symptoms observed in this case 
were undoubtedly due to the arrest of the bodily perspira- 
tion, because the effect of so extensive an application must 
be the same as that of varnishing the whole body. 

1 Neisser, Zeitschr. f. klin. Medicin, Bd. i., Heft 1. 



INDEX OF AUTHORS. 



Adamkiewicz, 112 
yEgenita, Paulus, 93 
Albers, 137, 148 
Alley, 79, 80 
Amory, 120, 125 
Apolant, 141 
Arndt, 169, 171 
Arnold, 205 
Arthaud, 117 
Ascherson, 80 
Aschoff, 162 
Auspitz, 112 



Badin, 102 

Baginski, A., 128 

Bailly, 36 

Baker, 59 

Balmanno Squire, 226 

Bamberger, 78 

Barbier, 44, 51, 134 

Bardenhewer, 216 

Barella, 96 

Bartscher, 178 

Bauer, 90 

Baumann, 72 

Bazin, 48, 69, 95, 131, 204, 225 

Beau, 202 

Begin, 51 

Behrend, 28, 138 

Bell, Benjamin, 79 

Bengelsdorff, 67 

Bennet, S., 222 

Berenger Ferand, 60 

Berenguier, 47, 50, 120, 138, 153 

Bergeron, 96 

Berghmann, 179 

Bernard, 45 

Bessieres, 149 



Bianchi, B., 213 
Bill, 72 

Billroth, 140, 174, 181, 
Binswanger, 54 
Binz, 37, 93, 96, 190 
Bley, 162 
Boeck, 204 
Boeck, von, 88 
Bouchardat, 80, 145 
Bouchut, 52 
Bouisson, 187 
Bourneville, 195 
Bouvier, 199 
Brand, 139 
Brera, 109 
Bretet, 24 
Brieger, 42 
Briquet, 36, 37 
Brochin, 47 
Brown, 120, 170 
Brshesinsky, no 
Buckell, 103 
Burdach, 62 
Burkart, 145 
Busch, 72 



Cabot, 148 
Carnot, 52 
Chapman, 170 
Charcot, 56, 98 
Charvet, 21, 135 
Chassaignac, 151 
Chatin, 96 
Chevallier, 31 
C^ievandhr, 46 
Chouppe, 142 
Chrestien, 98 
Christison, 146 
Clark, 120, 125 
Clemens, 181, 182 



232 



INDEX OF AUTHORS. 



Clover, 175, 1S0 
Cogliesi, 213 
Corlieu, log 
Coullon, 162 
Curschmann, 108, 220 



Fothergill, 38 
Fournier, 80, 111 
Fraser, 161 
Frerichs, 148, 224 
Freudenberg, 41 
Frommann, 56 
Fiirstner, 168 



Da Costa, 140 
Damourette, 119, 125 
Dauboeuf, 33 
Davidson, 155 
Declat, 71 
Delioux, 57, 205 
De'marquay, 221 
Demme, 218, 220 
Denk, 34, 35 
Denonvilliers, 181 
Devergie, 98 
Dioscorides, 137 
Dorval, 109 
Duclos, 137, 222 
Dujardin-Beaumetz, 99 
Dupuytren, 136 
Duroy, 180 
Dworzak, 157 



Eder, 144 

Edwards, 76, 135 

Englemann, 80 

English Chloroform Committee, 175, 

179 
Esmarch, 175 
Eulenburg, 160 
Ewald, 93 



Faginoli, 37 
Falck, 94, 129, 203 
Fallopius, 197 
Falot, 202 
Falret, 120 
Federschmidt, 218 
Fiedler, 145 
Fischer, no 
Feischmann, 47, 159 
Flemming, 144, 146 
Fonssagrives, 103 
Forcke, 159 
Foucaud de l'Espagne, 59 



Galezowski, 151 

Gamberini, 55, 58 

Garraway, 33 

Gatumeau, 117 

Gauchet, 33, 37, 170 

Gellhorn, 169 

Gerrard, 154 

Girl, 43 

Glover, 115 

Gohlius, 203 

Golden, 154 

Golding, 149 

Goltdammer, 40 

Gowers, 125 

Graefe, A. von, 35, 141, 150, 160, 161 

Gregory, 161 

Grimaud, 62 

Grissac, 32, 35 

Gubler, 48, 155 

Guerard, 153 

Guisson, 55 

Guttmann, 122, 125 

Guyochin, 37 

Gwalter, 82 



H 

Hager, 30 
Hardy, 48 
Harles, 97 

Hebra, 48, 68, 80, 201 
Hegar, 192 
Heiberg, 187 
Heim, 97 
Heinlein, 4T 
Heinrich, 157 
Helbert, 204 
Hemming, 33 
Hennig, 64 

Hermann, 16, 204, 213 
Herpin, 86 
Heusinger, 34 
Hjaltelin, 100 



INDEX OF AUTHORS. 



233 



Hiffelsheim, 160 
Hildebrandt, 66 
Horing, 118 
Hoffmeier, 128 
Hollander, 191 
Holmgreen, 179 
Huet, 57 
Huter, 179, 189 
Hiitte, 117, 119 
Hufeland, 63 
Husband, 170 
Husemann, 77, 148 



Imbert-Gourbeyre, 94, 95, 97, 203 
Isambert, 28 
Itzstein, 212 



Jacobi, 201 
Jacobi, A., 128 
Jacquot, 207 
Jarisch, 228 
Johnson, 113 
Jolly, 167 
J6rg, 132 



K 



Kaltenbach, 192 
Kaposi, 227 
Kappeler, 174, 183 
Kidd, 183 
King, 30 
Kern, 168, 171 
Kleinhau-s, 69 
Koch, 92 

Kobner, 33, 154, 170 
Kohler, 43, 162 
Kohl, 63 
Kottmeyer, 76 
Kowalewski, 151 
Krosz, 117, 119, 127 
Kiistner, 73, 128 
Kussmaul, 80, 90 



Laborde, 119, 140, 151 

Lacombe, 128 



Ladendorff, 196 

Lahr, 145 

Laennec, 203 

Lallemand, 180 

Landsberg, 147 

Langenbeck, M., 200 

Langenbeck, von, 66, 73, 175 

Langenbuch, 75 

Laroche, 105 

Ledelius, 223 

Lefort, 184 

Legrand, 98 

Lemattre, 96 

Leube, 41 

Leven, 161 

Levinstein, 145 

Lewin, G., 78, 87, 91 

Lewin, L., 65, 90, 145, 157, 207, 212 

Leyden, 220 

Lichtheim, 42 

Liebermann, 226 

Liebreich, 115, 151, 166, 192 

Lightfoot, 38 

Lisfranc, 21, 63 

Lister, 76 

Litten, 26 

Loffler, 51 

Loehlein, 76 

Lohrisch, 216 

Losch, 218 

Lvicke, 74 

Lurmann, 40 

Lusanna, 1 53 



M 



Macnal, 94 
Maestri, 50 
Magitot, 55 
Marchand, 128, 130 
Marsh, 167 
Martin, 125, 211, 213 
Martindale, 217 
Mattison, 145 
Mayer, 24 
Mecklenberg, 108 
Melsens, 89 
Merat, 210 
Mialhe, 11, T3, 212 



Mitscherlich, 71, : 
Mogling, 208 
Monneret, 37, 52, 
Morganti, 97 
Mossop, 119 



33 
163 



234 



INDEX OF AUTHORS. 



Miiller, 39 
Mund, 31 
Munk, J., 2ii 



N 



Neisser, 229 

Nelaton, 103 

Nicol, 119 

Neumann, 56, 71, 123, 227 

Notel, 167 



Oberlander, 190 
Odier, 53 
Ohms, 221 
Olshausen, 74 
Orfila, 53 



Reiche, 158 

Reil, 166 

Reiner, 168 

Rezek, 66 

Richardson, 44, 166, 191 

Riche, 52 

Richet, 186 

Ricord, 105, 107 

Riegel, 39, 215 

Rieken, 138 

Riemer, 56 

Riess, 39 

Rilliet, 104, 114 

Ringer, Sidney, 155 

Rodet, 107 

Rohrig, 75 

Roser, 100 

Roller, 65 

Romberg, 59 

Ronchard, Simon de, 37 

Rose, 73, 113, 212 

Rosenbach, 89 

Rossbach, 47 



Paget, 182 

Pearson, 79, 90 

Pelvet, 119, 125 

Percival, 60 

Pereira, 62, 94, 156 

Perrin, 180 

Petit, 154 

Petitjean, 107, in, 113 

Petters, 69 

Picard, 149 

Pick, 194 

Pickel, 92 

Pidoux, 50, 133, 162 

Piorry, 37 

Pleische, 92 

Plouviez, 188 

Pluskal, 225 

Pratorius, 76 

Preusse, 72 

Purkinje, 46, 132 



Rabuteau, 106, 119 
Radziejewski, 78, 202 
Ranneft, 219 
Rayer, 48 

Recklinghausen, von, 175 
Regnard, 101, 103, 113 



Sanger, 219 
Saikowski, 89 
Samelsohn, 195 
Samter, 144 
Sander, 130, 194 
Sansom, 183 
Santlus, 107 
Scheinesson, 184 
Schlothauer, 46 
Scholer, 155 
SchrOter, 194 
Schroff, 23, 147, 156, 163 
Schweig, 116 
Schwerin, E., 224 
Schuchardt, 165, 222 
Schulle, 168, 170 
Schiitz, 15 
Schuhmacher, 39 
Schulz, 93, 96 
Schultze, M., 2r3 
Schwilgue, 64 
Scribonius Largus, 136 
Sedillot, 176 
Seitz, 215 
Senator, 10 
Shaw, 168 
Sieveking, 214 
Sigmund, 86 



INDEX OF AUTHORS. 



235 



Simon, A., 101, 103, 113 
Simpson, 214 
Skinner, 33, 43 
Smith, 124, 135 
Sobotka, 135 
Sommerbrodt, 141 
Sonnenburg, 176 
Spencer Wells, 212 
Spoerer, 189 
Stark, 125; 130, 197 
Steinheim, 168 
Stille, 161 
Strieker, 39 



Unna, 209 
Urbantschitsch, 195 



V 

Veiel, 118 

Vepan, 32 

Veyrieres, 195 

Virchow, 1, 6, 21, 54, 57 

Voisin, 120 



W 



Tanquerel des Planches, 59 

Taylor, 136 

Thielmann, 119 

Tralles, 136 

Traube, 153, 164, 166 

Trotzscher, 160 

Trousseau, 29, 97, 162 

Tully, 64 

Turnbull, 156 



Wade, 38 
Wagner, 74 
Weber, 218 
Wecker, 154 
Wegscheider, 128 
Werdermann, 60 
Werneck, 53, 62 
Wernich, 140, 169 
Wibmer, 44, 59, 98, 199 
Wilkinghoff, 134 
Wilkinson, 68 
Wilson, 154 
Wyss, 95 



U 



Ummethum, 77 



Yvonneau, 17b 



INDEX OF SUBJECTS. 



Acid, arsenious, 27, 92 

boracic 54 

carbolic, 71 

citric, 70 

chrysophanic, 226 

copaivic, 49 

hydrobromic, 38 

hydrochloric, 70 

hydrocyanic, 161 

nitric, 70 

picric, 215 

phosphoric, 70 

pyrogallic, 228 

salicylic, 38 

sulphuric, 70 

tannic, 64 

tartaric, 70 
Acids, 70 

Acne from bromide of potassium, 121 
iodide of potassium, no, 

112 
iron, 29 
Aconitia, 155 
^Ether, sulphuric, 192 
yEthylidene chloride, 192 
Aloes, 22, 197 
Alteratives, 77 
Alum, 51 

Ammonium chloride, 207 
Amygdalae amarae, 161 
Amyl nitrite, 194 
Antimony, tartarized, 27, 200 

sulphuretted, 13, 207 
Apomorphia, 24 
Aqua amygdal amar., 161 

calcis, 50 

chlorini, 222 

laurocerasi, 161 
Arguria, 55 
Arnica, 134 
Araroba, 226 



Arsenic, 92 

in bismuth, 52 
Atropia, 27, 149 
Auri chloridum, 98 

et sodii chloridum, 98 



B 

Balsam of copaiba, 47 

of Peru, .208 
Barium chloride, 63 
Belladonna, 153 
Benzole, 214 
Berberin, 44 

Bismuth subnitrate, 12, 52 
Boracic acid, 54 
Bromine, 121 

acne, 126 
cachexia, 126 
Bromism, 126 



Cade, oil of, 69 

Cadmium sulphate, 62 

Caffein, 148 

Calabar bean, 160 

Calomel, 13, 15, 78 

Camphor, 131 

Cannabis Indica, 147 

Cantharides, 222 

Carbolic acid, 71 

spray, 74 
urine, 74 

Carbolism, 72 

Cardol, 224 

Castor oil, 196 

Chelidonium, 44 

Chloral hydrate, 166 

Chlorate of potassium, 128 

Chloride of gold, 98 



238 



INDEX OF SUBJECTS 



Chlorine, 222 
Chloroform, 2, 20, 173 

death from, 174 
Chrysophanic acid, 226 
Chrysarobin, 226 
Citric acid, 70 
Cod-liver oil, 221 
Colchicum, 23, 162 
Colocynth, 198 
Colombo-root, 43 
Constitution, 2 

epidemic, 21 
Creasote, 44 
Cubebs, 50 



Eruptions from sulphur, 199 
veratria, 159 
Excitants, 131 



Fowler's solution, 24, 94 



Gamboge, 14 
Gold chloride, 98 

and sodium chloride, 98 



Digitalin, 166 
Digitalis, 23, 164 
Duboisia, 154 



H 



Habituation, 17 
Hydrargyrum, 77 
Hydroquinone, 8 
Hyoscyamia, 23 
Hyoscyamus, 148 



Eczema mercuriale, 81 

Elaterium, 14 

Ergotin, 65 

Eserin, 160 

Eruptions from anacardium, 224 
antimony, 200 
arsenic, 94 
atrjpia, 152 
balsam of Peru, 209 
belladonna, 153 
benzole, 2 1 5 
bitter almonds, 161 
bromide of potassium, 
. 120 

cantharides, 223 
chloral hydrate, 169 
chlorine, 222 
chrysarobin, 227 
cod-liver oil, 222 
croton oil, 200 
digitalis, 164 
hyoscyamus, 148 
iodine, 109 
ipecac, 204 
mezereon, 225 
morphia, 141 
opium, 137 
pyrogallic acid, 228 
quinine, 3 [ 
santonin, 214 



Idiosyncrasy, 5, 20 

chemical, 11 
idiopathic, 11 

Immunity, 16 

Individuality, 6 

Iodine, 27, 99 

acne, 109 

Iodism, 106 

Iodoform, 190 

Iron, 29 



Jaborandi, 215 



Lead, acetate of, 58 

cachexia, 16 
Lime-water, 50 



M 

Mercury, albuminate of, 78 
Mercurial peptone, 79 



INDEX OF SUBJECTS. 



Mercurial tremor, 91 
Mercury, 77 

Methylene bichloride, igi 
Morphia, 5, 24, 140 
habit, 142 
Musk, 132 



Quassia, 44 
Quinine, 30 



2 39 



N 

Narcotics, 134 
Napelline, 56 
Nitrate of silver, 54 



Ointments, 8 

Opium, 1, 20, 26, 134 
eating, 142 
eruptions, 137 



Resorcin, 



4i 



Salivation, mercurial, 84 
Salvia leaves, 67 
Santonin, 211 
Saturnism, 16 
Secale cornutum, 23 
Silver nitrate, 54 
Skin, changes in, 28 
Sodium chloride, 13 
Strychnia, 42 
Styrax, 209 
Sulphur, 199 



Phloroglucin, 8 

Phosphoric acid, 70 

Phosphorus, 99 

Physostigmia, 160 

Pilocarpin, 5, 217 

Picric acid, 215 

Pix liquida, 69 

Pomegranate root, 23 

Potassium bromide, 27, 116 
chlorate, 128 
chloride, 130 
iodide, 27, 104 
sulphate, 131 

Predisposition, transitory, 15 

Pruritus opii, 137 

Pyrocatechin, 8 

Pyrogallic acid, 228 



Tannin, 25 
Temperaments, 7 
Tonics, 29 
Turpentine oil, 45 



Valerian, 133 
Veratria, 158 



Zinc oxide, 61 
lactate, 61 



